bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of vasopressin on cardiovascular changes during hemorrhage in conscious rats
Authors: Fujisawa Y. , Miyatake A. , Hayashida Y. , Aki Y. , Kimura S. , Tamaki T. , Abe Y.
Published: December 2017

Hypotensive hemorrhage decreases heart rate (HR) and renal sympathetic nerve activity (RSNA). Hemorrhage is a potent stimulus for arginine vasopressin (AVP) release; therefore, AVP may contribute to such inhibitory action of HR and RSNA during hemorrhage. We evaluated the roles of vasopressin on the regulation of blood pressure (BP), HR, and RSNA during hemorrhage using nonpeptide and selective V1- and V2-receptor antagonists (OPC-21268 and OPC-31260) in conscious rats. After hemorrhage (20 ml/kg body wt) BP decreased by 62 +/- 10 mmHg along with bradycardia (-110 +/- 15 beats/min) and renal sympathoinhibition (-50 +/- 8). Pretreatment of V1-receptor antagonist (5 mg/kg iv) did not affect the initial fall of BP but attenuated subsequent BP recovery. Bradycardic and renal sympathoinhibitory responses following hemorrhage were abolished (-14 +/- 24 beats/min and -7 +/- 9) by V1-receptor antagonist. Pretreatment of V2-receptor antagonist (1 mg/kg iv) did not affect the response of BP; however, it did slightly strengthen bradycardia and prolong renal sympathoinhibition. Hemorrhage increased the plasma AVP concentration more than 50-fold. These results indicate that when the plasma concentration of AVP is extremely high during hemorrhage, vasopressin via V1 receptor contributes to BP recovery by the peripheral vasoconstriction and exerts an inhibitory action on RSNA, and vasopressin via V2 receptor exerts opposite stimulatory action on RSNA.
Changes in ovine renal sympathetic nerve activity and baroreflex function at birth
Authors: Segar J. L. , Mazursky J. E. , Robillard J. E.
Published: December 2017

The purposes of this study were to characterize the changes in renal sympathetic nerve activity (RSNA) and baroreflex function at birth in conscious sheep. One hour after delivery by cesarean section, RSNA increased by 239 +/- 24% compared with fetuses. The upper and lower plateau values of the baroreflex function curves for RSNA, expressed as the percent maximum achieved in the fetus, were greater (P < 0.05) at 1 h (260 +/- 41 and 142 +/- 40%) and 5 h of age (254 +/- 34 and 100 +/- 19%) than in fetuses (100 and 10 +/- 3%), respectively. Curve midpoint pressures also were higher (P < 0.05) at 1 h (62 +/- 3 mmHg) and 5 h (66 +/- 4 mmHg) than in fetuses (51 +/- 2 mmHg). No changes in the sensitivity (gain) of the RSNA response to baroreceptor stimulation were seen. The baroreflex response curves for heart rate showed similar increases in the curve midpoint pressures, while gain did not change. To determine whether the high circulating levels of angiotensin II (ANG II) in the newborn period contribute to the rise in RSNA or the resetting of the baroreflex toward higher pressures, the angiotensin-converting-enzyme inhibitor, enalaprilat, was administered to five lambs before delivery. No differences in the increase in RSNA after birth were detected between control and treated animals. The curve midpoint pressures of both the RSNA and heart rate baroreflex response curves were significantly less (P < 0.05) in the treated compared with control lambs.(ABSTRACT TRUNCATED AT 250 WORDS)
Dietary sodium and central vs. peripheral ouabain-like activity in Dahl salt-sensitive vs. salt-resistant rats
Authors: Leenen F. H. , Harmsen E. , Yu H.
Published: December 2017

To assess the possible contribution of brain ouabain-like activity (OLA) to the pressor effects of high-sodium intake in Dahl salt-sensitive (Dahl S) rats, we assessed the effects of high (8%) on blood pressure (BP) and peripheral and brain OLA in Dahl on blood pressure (BP) and peripheral and brain OLA in Dahl S and Dahl salt-resistant (Dahl R) rats. On regular sodium intake, Dahl S and R had similar BP; however, by 7 wk of age adrenal and plasma OLA were 15–30% higher in Dahl S vs. R, whereas central OLA remained similar. On high-sodium intake, in Dahl S both peripheral and central OLA increased within 1 wk with additional increases after 3 wk. These increases preceded the rise in BP. In Dahl R rats, high sodium did not increase BP. However, 3 wk of high sodium did increase peripheral as well as central OLA, the latter to a lesser extent compared with Dahl S and not in the hypothalamus. These results are consistent with the concept that central OLA may be involved in the pressor responses to high sodium in Dahl S. Circulating OLA may play a role in the regulation of renal function to excrete excess sodium in both strains.
Vagal-induced tachycardia: release of vasoactive intestinal peptide and peptide HI
Authors: Anderson F. L. , Kralios A. C. , Cluff N. , Hanson G. R.
Published: December 2017

The relationship between vagal-induced tachycardia (VT) and release of vasoactive intestinal peptide (VIP) and peptide HI (PHI) into cardiac lymph and coronary sinus blood was studied in 23 alpha-chloralose-anesthetized open-chest dogs that were autonomically decentralized and pretreated with atropine and propranolol. After simultaneous right and left cervical vagal stimulation at 5 V, 20 Hz for 3 min mean +/- SE, increase in heart rate was 38 +/- 6 beats/min, and increase in lymph VIP output from control was 0.308 +/- 0.093 pg/min (P = 0.004). The decrease in VIP arterial minus coronary sinus concentration was not significant. The increase in heart rate did not significantly correlate with increase in lymph VIP output (R2 = 0.141) or decrease in VIP arterial minus coronary sinus concentration (R2 = 0.059). The increases in heart rate and lymph VIP output were blocked by hexamethonium. Increase in lymph PHI output from control during VT (5 dogs) was 0.797 +/- 0.658 pg/min. Arterial-coronary sinus PHI concentration difference did not change in these dogs. These data indicate that VT is associated but not significantly correlated with VIP and PHI release into cardiac lymph. Cholinoceptive nicotinic receptors may mediate VIP release and VT in anesthetized dogs.
Cilazapril treatment depresses ventricular function in spontaneously hypertensive rats
Authors: Christe M. E. , Perretta A. A. , Li P. , Capasso J. M. , Anversa P. , Rodgers R. L.
Published: December 2017

The purpose of this study was to characterize the effect of chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor on left ventricular function in spontaneously hypertensive rats (SHR). Cilazapril (5 mg/kg) was administered in the drinking water continuously for 11 wk, beginning at 4 wk of age. Systolic arterial pressure (SAP) was monitored weekly. At the end of the 11-wk period, left ventricular function was quantified using the perfused working heart preparation. Cilazapril exerted a rapid, complete, and persistent antihypertensive effect in the SHR in vivo but had no effect on SAP in the normotensive Sprague-Dawley (S-D) group. Nevertheless, the drug reduced left ventricular weight to the same extent in both strains. Function of untreated SHR hearts was not different from that of the untreated S-D hearts. Cilazapril treatment depressed heart performance (28–35%) in SHR but had no effect in the S-D group. The decline in pump performance in SHR hearts was associated with diminished tension development and velocity of shortening of papillary muscles. These results demonstrate that an ACE inhibitor, administered to young SHR, produces a reduction in left ventricular contractile function, which may be due to a decline in muscle contractility and which cannot be explained exclusively by the reduction in left ventricular mass.
Mapping myocardial activation distributions using neural networks: 2-D simulation results
Authors: Nelson T. R. , Boone J. M.
Published: December 2017

The goal of this study was to explore the capabilities of neural networks to map with accuracy the sequence and location of myocardial activation using QRS complexes simulating normal and altered activation. A two-dimensional (2-D) fractal-based computer model of myocardial activation was used to develop training data for initial network learning. Two types of activation scenarios were used to evaluate network learning: 1) 450 training sets based on three activation foci per set using randomly chosen times and activation sites, and 2) 199 training sets based on a sequential, hierarchical blocking of the fractal-based model conduction network. Network learning was evaluated with training and test cases using trained weights. Network-calculated activation maps compared with the target activation maps had a mean error of < 5% in assigning the site and timing of activation. Pointwise mean correlation coefficients were > 0.98 for all conduction network cases and > 0.84 for the more demanding point foci cases. We conclude, based on these simulation results, that neural networks may be used to calculate activation maps using electrocardiogram lead data for a variety of activation patterns.
Increases in local cerebral blood flow associated with somatosensory activation are not mediated by NO
Authors: Adachi K. , Takahashi S. , Melzer P. , Campos K. L. , Nelson T. , Kennedy C. , Sokoloff L.
Published: December 2017

Effects of inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME) on the increases in local cerebral blood flow (LCBF) produced in the whisker-to-barrel sensory pathway by vibrissal stimulation were studied in conscious rats with the autoradiographic iodo[14C]antipyrine method. Unilateral whisker stroking increased LCBF in the ipsilateral trigeminal spinal and principal sensory nuclei, contralateral ventral posteromedial thalamic nucleus, and contralateral somatosensory barrel cortex. Intravenous L-NAME (30 mg/kg) lowered baseline LCBF without altering the percent increases due to stimulation. Intracisternal infusions of L-NAME in doses about 10 times the molar content of free arginine in brain inhibited brain NO synthesis activity by 88%, but the percent augmentations of LCBF by stimulation remained unchanged. Chronic treatment with L-NAME (50 mg/kg ip twice daily for 4 days) inhibited NO synthase activity in brain by 84% but also failed to reduce the percent increases in LCBF due to stimulation. These results indicate that NO does not mediate the increases in LCBF associated with functional activation.
Buffering of respiratory variations in venous return by right ventricle: a theoretical analysis
Authors: Santamore W. P. , Amoore J. N.
Published: December 2017

The role of the right ventricle (RV) in buffering systemic venous return, thereby dampening respiratory-induced variations, left ventricular (LV) stroke volume, and systemic arterial pressure variations was examined using a computer model of the cardiovascular system. Respiration was simulated by cyclical variations in intrathoracic and abdominal pressures (cycle time 5 heartbeats), causing a 43-ml fluctuation in venous return per heartbeat (mean 71 ml) compared with fluctuations of 19 ml in RV stroke volume, 6 ml in pulmonary venous flow, and only 3 ml in LV stroke volume. On a percentage basis, the RV provided 56% of the total buffering of systemic venous return, the lungs another 30%, whereas the LV only 7%. A 10-fold increase in RV diastolic compliance increased the RV stroke volume variations from 26 to 57% of the venous return variations; a 10-fold increase in RV elastance increased them from 24 to 60%, whereas decreasing pulmonary arterial pressure from 28 to 10 mmHg increased them from 28 to 56%. The results also suggest that an underrecognized function of the RV is to buffer systemic venous return and thereby keep LV stroke volume relatively constant.
Nonsynchronous changes in myocardial collagen mRNA and protein during aging: effect of DOCA-salt hypertension
Authors: Besse S. , Robert V. , Assayag P. , Delcayre C. , Swynghedauw B.
Published: December 2017

Myocardial fibrosis has been investigated in 3-, 16-, and 24-mo-old normal rats and also in 24-mo-old rats subjected to deoxycorticosterone acetate (DOCA)-salt treatment-induced-hypertension. Collagen content was assessed both histologically and by hydroxyproline assay. Type I and III procollagen mRNA levels were quantitated by Slot Blot analyses. Aging is associated with fibrosis as shown both biochemically (hydroxyproline concentration in 3-, 16-, and 24-mo-old rats was 0.70 +/- 0.05, 0.92 +/- 0.07, and 1.57 +/- 0.13 mg/g of left ventricle, respectively, P < 0.05 and P < 0.0001 vs. 3 mo) and histologically. By contrast, type I procollagen mRNA levels decreased during aging (from -63%, P < 0.001 in 16-mo-old rats and -51%, P < 0.01 in 24-mo-old rats vs. 3-mo-old rats) as well as type III procollagen mRNA levels. DOCA-salt treatment in 24-mo-old rats had no effect on either the degree of fibrosis or the mRNA levels. We conclude that nonsynchronous changes in myocardial collagen mRNA and protein occur during aging, indicating translational and/or posttranslational mechanisms in collagen regulation. Hypertension during senescence did not modify collagen deposition at either the protein or mRNA levels.
Effects of oral AVP receptor antagonists OPC-21268 and OPC-31260 on congestive heart failure in conscious dogs
Authors: Naitoh M. , Suzuki H. , Murakami M. , Matsumoto A. , Arakawa K. , Ichihara A. , Nakamoto H. , Oka K. , Yamamura Y. , Saruta T.
Published: December 2017

Rapid right ventricular pacing could induce congestive heart failure in conscious dogs with significant increase in plasma concentration of arginine vasopressin (AVP) (from 1.2 +/- 0.2 to 3.4 +/- 0.6 pg/ml). In this experimental model of heart failure, oral administration of the selective AVP V1 receptor antagonist OPC-21268 significantly increased cardiac output and improved renal function without significant changes in serum electrolytes and hormones. Oral administration of the selective AVP V2 receptor antagonist OPC-31260 induced marked water diuresis, which resulted in significant increases in serum sodium concentration, plasma renin activity, and plasma concentration of AVP, although it did not produce hemodynamic improvement. Combined administration of OPC-21268 and OPC-31260 showed supra-additive hemodynamic responses as well as additive renal and metabolic responses, i.e., it showed prolonged decrease in mean arterial pressure and profound increase in cardiac output. These results suggest that AVP plays a significant role in elevation of vascular tone through V1 receptors and plays a major role in retaining free water through V2 receptors in this model of heart failure. Furthermore, combined administration of V1 and V2 receptor antagonists could induce not only metabolic and hormonal responses but also more beneficial hemodynamic responses than those observed following treatment with V1 receptor antagonist alone.
Perinatal accumulation of arterial wall constituents: relation to hemodynamic changes at birth
Authors: Bendeck M. P. , Keeley F. W. , Langille B. L.
Published: December 2017

We compared arterial growth to hemodynamic changes in the perinatal period in lambs. Blood pressure did not change significantly from 120 days gestation to 3 days postpartum, when it was 45.4 +/- 1.9 mmHg; however, pressure rose to 64.8 +/- 2.5 mmHg at 21 days postpartum. Thoracic and abdominal aortic and iliac and carotid arterial blood flows fell > 50% after birth but returned to fetal levels except in the abdominal aorta by 21 days postpartum. Blood flows in mesenteric (BFm) and renal (BFr) arteries increased between 120 days gestation (BFr = 13.4 +/- 1.4; BFm = 41.8 +/- 3.5 ml/min) and 140 days gestation (BFr = 25.9 +/- 1.8; BFm = 189 +/- 18 ml/min) and between 3 and 21 days postpartum (to BFr = 71.1 +/- 14.3; BFm = 334 +/- 59 ml/min). Elastin accumulation accelerated at 140 days gestation in all arteries except the thoracic aorta, in which elastin accumulation was always rapid. Collagen but not DNA accumulation also accelerated in most arteries. Postpartum dexamethasone (0.1 mg/kg twice a day) did not affect abdominal aortic elastin by 10 days of age (23.9 +/- 2.7 vs. 26.4 +/- 4.1 mg for controls); however, dexamethasone upregulated tropoelastin mRNA in fetuses. We hypothesize that cortisol stimulates elastin accumulation in late gestation. Postnatal elastin but neither collagen nor DNA correlated with blood flow changes at birth (r = 0.855, P < 0.05). We infer that accumulation of elastin is sensitive to blood flow rates during perinatal development.
Vulnerability of conducted vasomotor response to ischemia
Authors: Lin Y. , Duling B. R.
Published: December 2017

Many vasoactive substances induce two responses, a direct effect at the site of application and a conducted response that spreads along the vessel length. In the microcirculation, we find that these two components of the vasomotor response display quite different sensitivities to occlusion and/or ischemia. Conducted vasomotor responses were induced in arterioles of the hamster cheek pouch by micropipette application of two test agents: phenylephrine (PE), which causes a receptor-mediated vasomotor response, and KCl, which causes an alteration in the membrane potential by a simple change in the K+ gradient. Ischemia was produced either by total occlusion of the vascular supply, which resulted in a complete cessation of flow in all vessels, or by venous occlusion, which was achieved by gradually inflating a pressurized cuff positioned across the pedicle of the pouch until venous return from the pouch was arrested while the feed arterioles remained patent. Both types of occlusion produced ischemia, the former with low intravascular pressure, the latter with high intravascular pressure. During both types of occlusion, arterioles were initially maximally dilated and unresponsive to both agonists, but over a subsequent 3- to 5-min period, resting arteriolar tone and local responses to both agonists returned. With total occlusion, the conducted response to KCl returned in parallel with the local response, whereas the conducted response to PE was diminished or absent. With venous occlusion, the local responses recovered as with total occlusion, but the conducted responses to both PE and KCl recovered as well.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of cardiac output distribution on cardiac filling pressure during rest and dynamic exercise in dogs
Authors: Sheriff D. D. , Zhou X.
Published: December 2017

The distribution of cardiac output (CO) between compliant and noncompliant organs is an important determinant of the slope of the relationship predicted between CO and right atrial pressure (RAP). However, curves relating CO to RAP at rest are shifted rightward (higher CO) and upward (higher RAP) by exercise with no change in slope, despite a large rise in the fraction of CO directed to noncompliant muscle vasculature, which is predicted to decrease the slope. We sought to test whether reductions in CO imposed during rest and exercise are accompanied by changes in its distribution that would favor constant slopes. Six dogs had atrioventricular block produced surgically and had blood flow transducers implanted on the ascending aorta and the terminal aorta. Total muscle blood flow (MBF) was estimated from terminal aortic flow by assuming that all of the increase in CO in mild dynamic exercise is directed to muscle. CO was reduced by lowering ventricular pacing rate at rest and during graded treadmill exercise (2 and 4 miles/h at 0% grade). Exercise increased the fraction of CO directed to muscle (MBF/CO) (P < 0.001). The effect of changes in CO on MBF/CO depended on exercise intensity (P < 0.01). At rest, MBF/CO fell from 0.53 to 0.45 when CO was reduced; this is expected to reduce the slope of the measured relationship between CO and RAP. During exercise at 2 miles/h, MBF/CO changed little when CO was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
A monoclonal antibody to P-selectin ameliorates injury associated with hemorrhagic shock in rabbits
Authors: Winn R. K. , Paulson J. C. , Harlan J. M.
Published: December 2017

P-selectin (CD62P) can participate in leukocyte rolling when it is expressed on the surface of endothelial cells. We examined the role of CD62P in hemorrhagic shock and resuscitation. Rabbits were treated with saline, an anti-CD62P (alpha-CD62P) monoclonal antibody (MAb; PB1.3), an isotype-matched MAb (PNB1.6), or an alpha-CD18 MAb (60.3). Catheters were placed in the femoral artery and vein for monitoring, and cardiac output was then reduced to 33% of baseline for 1.5 h. Shed blood was returned, and resuscitation was continued to maintain the cardiac output to within 90% of baseline. There were no statistical differences between the saline- and MAb PNB1.6-treated groups; they were therefore combined into a control group. The MAb PB1.3- and MAb 60.3-treated groups required significantly less fluid resuscitation than the controls (12, 17, and 56 ml/kg, respectively). We conclude that MAbs directed to functional epitopes of either CD62P or CD18 provide significant protection from vascular injury after hemorrhagic shock.
Early disturbance of baroreflex control of heart rate after tail suspension in conscious rats
Authors: Martel E. , Lacolley P. , Champeroux P. , Brisac A. M. , Laurent S. , Cuche J. L. , Safar M. E.
Published: December 2017

Experiments were performed on conscious chronically instrumented rats maintained on tail suspension to determine the time course of changes in baroreceptor control of heart rate produced by this procedure. Pressor responses were elicited by bolus injections of graded doses of phenylephrine and sodium nitroprusside, permitting evaluation of the totality of the sigmoidal curve relating mean arterial pressure to heart rate. Compared with control rats maintained at 0 degrees, rats maintained at 20 degrees using tail suspension for 24 h showed a significant reduction in reflex gain (-3.9 +/- 0.1 vs. -5.8 +/- 0.3 beats/min; P < 0.001) together with a reduction in the upper (472 +/- 11 vs. 512 +/- 5 beats/min; P < 0.01) and lower (270 +/- 3 vs. 284 +/- 2 beats/min; P < 0.01) plateaus of the sigmoidal curve. In three groups of rats, the sigmoidal curve was studied successively after returning for 1, 24, and 48 h at 0 degrees. The observed change in the gain of the reflex returned toward control values after 48 h, whereas the other parameters characterizing the sigmoidal curve did not change significantly. Transient but significant modifications of heart rate (tachycardic response) after the immediate return to the horizontal position were observed. The study provides evidence that 1) a significant change of the totality of the sigmoidal curve characterizing baroreceptor control of heart rate occurs very early after tail suspension in rats and 2) the gain of the reflex is restored during the 48 h after release of tail suspension, whereas the other parameters characterizing the curve, particularly the plateaus, remain altered.
Capillary pressure, pulse pressure amplitude, and pressure waveform in healthy volunteers
Authors: Shore A. C. , Sandeman D. D. , Tooke J. E.
Published: December 2017

The influence of gender, local temperature, and systemic blood pressure on human capillary pressure is unknown. Finger nail fold capillary pressure was therefore directly measured in 74 healthy supine volunteers (40 female) at midaxillary level. Capillary pressure was lower in women than in men (15.9 +/- 3.0 vs. 18.2 +/- 2.3 mmHg; P = 0.001), particularly in premenopausal women, but was not related to systolic, diastolic, or mean blood pressure. Capillary pulse pressure amplitude was related to skin temperature, an effect more marked in women (P = 0.003). There was a significant association between skin temperature and the time taken for the systolic pressure rise to reach the capillary, in women only (r = -0.69, P < 0.001). Increasing age reduced the high-frequency waves in the pressure waveform [2nd harmonic percentage of fundamental: r = -0.52 and P = 0.002 (women), r = -0.52 and P = 0.004 (men)]. Thus mean capillary pressure and the pressure waveform may be influenced by gender, age, and skin temperature, illustrating the necessity to adequately match control groups during assessments of capillary pressure pathophysiology.
Cardiorespiratory reflex control in rats with left ventricular dysfunction
Authors: Jung R. , Dibner-Dunlap M. E. , Gilles M. A. , Thames M. D.
Published: December 2017

Patients with heart failure exhibit a neurohumoral excitatory state and abnormal baroreflex control of the cardiovascular system. We determined whether arterial baroreflexes are impaired during left ventricular dysfunction (LVD) caused by chronic myocardial infarction in the absence of congestive heart failure and whether abnormal central mechanisms contribute to this impairment. Baroreceptors were stimulated in anesthetized rats with and without LVD by increasing arterial pressure with phenylephrine. Lumbar sympathetic nerve and phrenic nerve activity as well as heart rate were recorded. Rats were divided into different groups based on infarct size. Rats with moderate LVD showed impaired baroreflex control of sympathetic, ventilatory, and heart rate responses. Baroreflex gains were inversely related to the size of the infarct. The central gain for sympathetic nerve activity, obtained by using electrical stimulation of the aortic depressor nerve, also was impaired. Baroreflex control of the cardiorespiratory system is thus impaired in rats with moderate LVD in the absence of congestive heart failure. The attenuated baroreflexes are likely due to abnormal afferent mechanisms, although central mechanisms contribute to the impaired barosympathetic reflex.
Inhibition of nitric oxide synthesis does not affect ischemic preconditioning in isolated perfused rat hearts
Authors: Weselcouch E. O. , Baird A. J. , Sleph P. , Grover G. J.
Published: December 2017

Endothelium-derived nitric oxide (NO) has recently been reported to be a mediator of ischemic preconditioning in dog hearts. The aim of the present study was to determine the role of NO in ischemic preconditioning in isolated perfused rat hearts. Rat hearts were perfused at either constant pressure (80 mmHg) or constant flow. After aerobic perfusion (37 degrees C) for 10 min, hearts were treated with N omega-nitro-L-arginine methyl ester (L-NAME; 30 microM), which is an inhibitor of NO synthase, or vehicle. Ten minutes later, the hearts were preconditioned (4 episodes of 5 min of global ischemia and 5 min of reperfusion) or perfused normally before a 30-min global ischemic period. All hearts were reperfused for 30 min. Coronary flow or perfusion pressure plus heart rate and contractile function were measured continuously. Hearts perfused at constant pressure and treated with 30 microM L-NAME, a concentration that effectively inhibits endogenous NO synthesis, exhibited decreased coronary flow after 10 min, and flow remained decreased throughout the experiment. Ischemic preconditioning before 30 min of global ischemia resulted in a doubling of contractile function and a reduction of lactate dehydrogenase release at the end of the 30-min reperfusion period compared with nonpreconditioned hearts. The protective effect of preconditioning was not different in L-NAME-treated hearts. In addition, inhibition of NO synthase had no effect on the severity of ischemia in nonpreconditioned hearts. Similar results were obtained in preconditioned hearts that were perfused at constant flow, indicating that the flow reductions caused by L-NAME did not influence the results.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of oxygen-derived free radicals in canine reperfusion arrhythmias
Authors: Euler D. E.
Published: December 2017

The role of oxygen-derived free radicals in reperfusion arrhythmias was investigated in open-chest anesthetized dogs. The left anterior descending coronary artery was cannulated and perfused by an arterial bypass shunt. Ischemia was produced for 15 min by shunt occlusion and retrograde diversion of collateral blood flow. Dogs (n = 12) were treated with saline, N-(2-mercaptopropionyl)glycine (50 mg/kg), deferoxamine (10 mg/kg), superoxide dismutase (15,000 U/kg) plus catalase (55,000 U/kg), or dimethylthiourea (500 mg/kg). All agents were infused intravenously for 1 h starting 30 min before occlusion and continuing for 5 min of reperfusion. There were no differences in mean arterial blood pressure, heart rate, antegrade coronary flow, retrograde coronary flow, or size of the risk region among the five treatment groups. None of the dogs developed ventricular fibrillation during occlusion, whereas 88% of the 60 dogs fibrillated upon reperfusion. The antioxidant interventions did not alter the incidence of reperfusion-induced ventricular fibrillation compared with the saline-treated controls. The results suggest that free radicals do not play a role in lethal canine reperfusion arrhythmias.
Changes in endothelial actin cytoskeleton at leakage sites in the rat mesenteric microvasculature
Authors: Thurston G. , Baldwin A. L. , Wilson L. M.
Published: December 2017

The purpose of the present study was to compare the endothelial actin cytoskeleton at sites of inflammation-induced macromolecular leakage with that of intact endothelium. The circulation of a selected mesenteric window of anesthetized rats was perfused for 3 min with histamine (100 microM) plus fluorescein isothiocyanate (FITC)-albumin, or FITC-albumin alone, and was fixed at physiological pressure. The vasculature was then perfusion stained with rhodamine phalloidin to label filamentous actin (F-actin) and examined with a confocal microscope. The leakage sites were divided into three categories based on the extent of FITC-albumin leakage: 1) focal leaks, 2) mid leaks, and 3) extended leaks. The leaks were identifiable with a particular endothelial cell(s), and the structure of the endothelial actin cytoskeleton was characterized at these sites. Focal leaks occurred along a small region of endothelial cell-cell contact and in most observed cases were located at a region of specific disruption of the endothelial peripheral actin rim (PAR). Mid leaks involved the disruption of one endothelial cell, and the affected cell was observed to have extended disruption of the PAR as well as increased diffuse F-actin staining throughout the cell (1.9-fold increase relative to adjacent cells). Extended leaks involved the disruption of two or more adjacent endothelial cells, and each cell exhibited an actin pattern similar to that seen at mid leaks. These results show that histamine-induced macromolecular leakage in situ is associated with significant changes in the endothelial actin cytoskeleton.
Effects of nifedipine on vascular waterfall and arterial resistance in canine hindlimb
Authors: Shrier I. , Magder S.
Published: December 2017

Pressure-flow relations in the canine hindlimb can be well explained by a vascular waterfall at the arteriolar level. Under these conditions, P(art) = Pcrit + Q.Rart, where P(art) is the arterial pressure, Pcrit is the waterfall pressure, Q is regional flow, and Rart is the arterial resistance of the vessels upstream from the waterfall. To determine whether calcium channels in vascular smooth muscle affect Pcrit in addition to Rart, we pump perfused canine hindlimbs and measured both variables over a range of perfusion pressures (Pper) before and during the infusion of the calcium channel blocker nifedipine. Nifedipine significantly decreased Pcrit and Rart at each Pper. Increasing Pper under control conditions from 50 to 150 mmHg significantly increased Pcrit from 24.2 +/- 1.5 to 42.5 +/- 2.2 mmHg. During nifedipine infusion, increasing Pper from 25 to 100 mmHg also increased Pcrit from 14.5 +/- 1.5 to 20.2 +/- 1.9 mmHg, but the rate of increase was less. In contrast to the rise in Pcrit with increasing Pper, Rart significantly decreased from 10.7 +/- 1.1 to 8.1 +/- 1.2 mmHg.min.100 g.ml-1 before nifedipine infusion, and from 5.7 +/- 0.4 to 2.2 +/- 0.1 mmHg.min.100 g.ml-1 during nifedipine infusion. Venous resistance (Rven) significantly decreased with increases in Pper and during nifedipine infusion. The regional elastic recoil pressure (Pel, a measure of small venular pressure) increased with both an increase in Pper and nifedipine. These results suggest that nifedipine decreases Pcrit, Rart, and Rven and that at constant Pper nifedipine increases Pel.
Compensated coronary microvascular growth in senescent rats with thyroxine-induced cardiac hypertrophy
Authors: Tomanek R. J. , Connell P. M. , Butters C. A. , Torry R. J.
Published: December 2017

We tested the hypothesis that coronary angiogenesis in response to chronic thyroxine (T4) treatment is not limited by age. Male Fischer 344 rats aged either 8 (young adult) or 24 (senescent) mo were studied after receiving either L-thyroxine (0.2 mg/kg sc) or vehicle for 2 mo. Heart weight-to-body weight ratio, compared with age-matched controls, increased by 47 and 44% in 8- and 24-mo T4 groups, respectively. Maximal myocardial perfusion per unit mass, measured in diastole-arrested, maximally dilated, isolated hearts, was similar in T4 rats and their age group controls; however, flow tended to be lower in senescent than in young adult rats. Thus the cross-sectional area of the coronary vessels grew in proportion to the increase in cardiac mass. Morphometric analyses, based on image analysis, showed that capillary length density was slightly lower in the midmyocardium but not the epimyocardium of the 24-mo T4 group compared with their age group controls. However, volume density, surface density, and intercapillary distance were not influenced by T4 treatment and the presence of cardiac hypertrophy. We conclude that in this model of cardiac hypertrophy 1) coronary vessel growth parallels the increase in ventricular mass, 2) capillaries grow by proliferation and an increase in diameter, and 3) vascular growth is not notably compromised during senescence.
Role of endogenous endothelin in normal hemodynamic status of anesthetized dogs
Authors: Teerlink J. R. , Carteaux J. P. , Sprecher U. , Loffler B. M. , Clozel M. , Clozel J. P.
Published: December 2017

Endothelin (ET) is a potent vasoconstrictor that may be involved in a number of cardiovascular disorders, although its role in normal hemodynamics remains unclear. Twenty-two anesthetized open-chest dogs were instrumented for measurement of systemic and pulmonary hemodynamics, cardiac output, coronary blood flow, and cardiac contractility. Big ET induced peripheral and coronary vasoconstriction, which occurred before significant elevations in plasma ET and which was nearly completely blocked by bosentan, a new nonpeptidic mixed (ETA and ETB) ET receptor antagonist. Bosentan also prevented the peripheral dilatation caused by the specific ETB receptor agonist, sarafotoxin S6c, but did not prevent the peripheral vasoconstriction induced by angiotensin II. Bosentan alone had no significant hemodynamic effect in the normal anesthetized dog, although it did induce a reactive increase in the plasma level of ET-1 and ET-3. This study demonstrates that, despite blocking both ETA and ETB receptors, bosentan alone had no hemodynamic effect, suggesting that ET does not play a major role in the normal hemodynamic status of anesthetized dogs.
Noninvasive measurement of ascending aortic blood velocity in mice
Authors: Hartley C. J. , Michael L. H. , Entman M. L.
Published: December 2017

Mice are useful models in numerous research protocols, but monitoring cardiovascular parameters in small animals is difficult. Therefore we evaluated the use of 20-MHz pulsed Doppler ultrasound to measure ascending aortic blood velocity in intact anesthetized mice. Using a 0.5-mm-diameter 20-MHz transducer applied to the right sternal border, we recorded audio Doppler signals from the ascending aorta of 31 mice [24.4 +/- 1.5 (SD) g body wt]. The signals were played back at speed into a fast Fourier transform analyzer from which we measured heart rate (453 +/- 96 beats/min), ejection time (38 +/- 3%), peak velocity (90 +/- 11 cm/s), mean velocity (23 +/- 4 cm/s), rise time (7.3 +/- 2 ms), stroke distance (29 +/- 7 mm), and acceleration (163 +/- 63 m/s2) from the spectral envelopes. We determined aortic diameter (1.2 +/- 0.2 mm) and Doppler angle (0–20 degrees) in six mice by molding the aortic root and major systemic vessels with casting resin infused at 100 mmHg pressure. For an aortic diameter of 1.2 mm, cardiac output was estimated to be 14.8 ml/min and stroke volume to be 33 microliters. To verify the origin of the signals and to test responsiveness to known stimuli, we measured velocity signals from the aorta and other nearby vessels and varied heart rate and aortic velocity by warming or by infusion of isoproterenol in three open-chest animals. For the noninvasive applications, acoustic coupling was adequate through the moistened fur, and aortic velocity signals were obtained in all animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line
Authors: Ashen M. D. , O'Rourke B. , Kluge K. A. , Johns D. C. , Tomaselli G. F.
Published: December 2017

We have cloned the human homologue of the inward rectifier K+ channel from both heart and brain tissue (HHBIRK1). The human clones were identical to each other in their coding regions and were highly homologous to the mouse macrophage (IRK1) channel. The inward rectifier currents from human and mouse clones were characterized using a novel strategy for stable ion channel expression in a human cell line. The permeability of the expressed inwardly rectifying channels was greater for K+ than for Rb+, whereas no current was observed when K+ was replaced by Na+. A prominent time- and voltage-dependent block was observed in the presence of Ba2+, whereas a small decay in the steady-state current was observed with millimolar concentrations of Na+. Single-channel conductances of 49.1 +/- 3.3 pS (n = 6) and 40.2 +/- 2.5 pS (n = 3) (P = 0.005) were obtained for the HHBIRK1 and IRK1 clones, respectively. These results indicate that sequence dissimilarities between human and mouse inward rectifier K+ channels may have significant functional consequences.
Vascular resistance and arterial pressure low-frequency oscillations in the anesthetized dog
Authors: Cevese A. , Grasso R. , Poltronieri R. , Schena F.
Published: December 2017

The spontaneous variability of heart rate and arterial blood pressure was investigated in chloralose-anesthetized dogs with the left iliac vascular bed mechanically uncoupled from the central circulation. Electrocardiogram, mean arterial pressure (ABP), iliac perfusion and venous pressures, and flow (FLOW) were recorded for 5 min in steady state. Autoregressive spectral and cross-spectral analyses and digital filtering were performed. The variation coefficient (VC%), calculated from the overall variance of each signal, was 5–7%, with the exception of perfusion pressure (VC% = 1%). The frequency-related percentage of total variance was distributed among three frequency bands: two were < 0.20 Hz [lower (F1) and higher (F2; low-frequency range = F1 + F2)], and one was > 0.20 Hz (respiratory, F3). F3 was not always present in RR, which, however, oscillated also in F1 and F2, although with limited amplitude; ABP showed large respiratory and low-frequency oscillations; the FLOW oscillations were in the low-frequency range. Cross-spectral analysis showed high squared coherence in the relevant frequency bands between variables in the three couples: RR-ABP, RR-FLOW, and ABP-FLOW. Changes in RR preceded changes in ABP and in FLOW by > or = 3 s, whereas FLOW was approximately in phase opposition to ABP. It was concluded that, in the chloralose-anesthetized dog, 1) arterial pressure and heart rate oscillate with frequencies corresponding to those described in conscious humans, 2) low-frequency arterial pressure oscillations are due to changes in peripheral vascular resistance, and 3) peripheral vascular resistance does not display respiratory oscillations. Furthermore it was suggested that oscillations of vasomotor tone are generated by a rhythm of central origin and that F1 and F2 oscillations may recognize a common mechanism.
Phenylephrine contracts rat tail artery by one electromechanical and three pharmacomechanical mechanisms
Authors: Chen X. L. , Rembold C. M.
Published: December 2017

There are at least four mechanisms hypothesized to account for excitation-contraction coupling in arterial smooth muscle. 1) Contractile agonists and changes in extracellular [K+] ([K+]o) induce contraction by depolarization, which increases Ca2+ influx; this is the only mechanism involving a change in membrane potential (Em). 2) Contractile agonists release Ca2+ from the intracellular Ca2+ store. 3) Contractile agonists increase Ca2+ influx without changing Em either by activating voltage-dependent L-type Ca2+ channels or by opening other Ca(2+)-permeable channels. 4) Contractile agonists increase intracellular Ca2+ ([Ca2+]i) sensitivity of force; this is the only mechanism that does not involve changes in [Ca2+]i. Each of these mechanisms has been demonstrated in intact, skinned, or dissociated smooth muscle preparations. However, these four mechanisms have not been compared in the same preparation. The goal of this study was to determine which of these four contractile mechanisms are physiologically relevant in the intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine and high [K+]o. We then measured Em with microelectrodes, [Ca2+]i with fura 2, and isometric force with a strain gauge transducer. We find that all four mechanisms contributed to phenylephrine-induced rat tail artery contraction. The majority of phenylephrine-induced contraction was caused by depolarization and by increases in the [Ca2+]i sensitivity of force. Low concentrations of phenylephrine also increased [Ca2+] independent of changes in Em, potentially by increases in Ca2+ influx. Release of Ca2+ from intracellular stores was only observed with high concentrations of phenylephrine. Smooth muscle appears to invoke multiple mechanisms for excitation-contraction coupling.
Role of spinal NK1 receptors in cardiovascular responses to chemical stimulation of the gallbladder
Authors: Pan H. L. , Bonham A. C. , Longhurst J. C.
Published: December 2017

The present study examined the role of substance P (SP) as a sensory neurotransmitter in cardiovascular responses to bradykinin applied on the gallbladder. Experiments were performed in anesthetized cats in which sympathetic chains were transected at the T5-T6 level, and the tip of the intrathecal catheter was positioned at T6-T7 to limit the injectate between T6 and L2. Bradykinin (10 micrograms/ml) was applied onto the gallbladder before and after intrathecal injection of [D-Pro2,D-Phe7,D-Trp9]SP (100–200 micrograms, NK1/NK2-receptor antagonist), CP-99,994 (50–100 micrograms, selective NK1 antagonist), MEN-10,376 (100–500 micrograms, selective NK2 antagonist), or vehicle. Intrathecal injection of NK1 but not NK2 antagonist significantly reduced increases in mean arterial pressure, heart rate, and maximal rate of left ventricular pressure change by 28 +/- 2 mmHg (33 +/- 4%), 4 +/- 1 beats/min (42 +/- 5%), and 497 +/- 46 mmHg/s (36 +/- 4%), respectively. Intrathecal injection of NK1 or NK1/NK2 antagonist had no effect on cardiovascular responses evoked by electrical stimulation in the rostral ventral lateral medulla. These data suggest that endogenous SP, acting as a sensory neurotransmitter, is involved in the excitatory cardiovascular reflex caused by chemical stimulation of the gallbladder through its action on NK1 receptors in the spinal cord.
Regional differences in IK density in canine left ventricle: role of IK,s in electrical heterogeneity
Authors: Gintant G. A.
Published: December 2017

Delayed rectifier K+ current (IK) was studied in isolated myocytes from canine left ventricular epicardium and midmyocardium using whole cell patch-clamp techniques. IK density during activation was greater in epicardial vs. midmyocardial myocytes [1.06 +/- 0.09 vs. 0.66 +/- 0.09 pA/pF (SE); P < 0.01] measured during 3-s depolarizing pulses to +25 mV. IK density was greater in epicardial myocytes at all times examined (range 150 ms to 3 s, +25 mV) and on termination of 3-s test pulses (potentials +5 to +65 mV). Greater IK density could not be explained by differences in activation kinetics or voltage dependence of activation. Two components of IK (IK,r and IK,s) have been described in guinea pig myocytes (Sanguinetti, M. C., and N. Jurkiewicz, J. Gen. Physiol. 96: 192–214, 1990). To assess whether differences in IK density could be ascribed to IK,r or IK,s, tail currents were fit to the sum of two decaying exponentials, with each component analogous to IK,s and IK,r based on sensitivity to E-4031 and rectification properties. Greater tail current density in epicardial myocytes was due to greater IK,s with no discernible difference in IK,r. These results suggest that regional differences in IK density in left ventricular epicardium are due to a larger IK,s component, which contributes to ventricular electrical heterogeneity and may reflect the differential expression of the IsK channel.
Nonlinear chaotic dynamics of arterial blood pressure and renal blood flow
Authors: Wagner C. D. , Persson P. B.
Published: December 2017

To determine whether arterial pressure (AP) and renal blood flow (RBF) are nonlinear dynamic processes (chaotic), we measured resting AP and RBF over 4 h in six conscious dogs. A catheter was placed in the aorta, and transit-time flowmeters were positioned around the renal artery. The average AP was 102 +/- 3 mmHg, and the mean RBF was 318 +/- 42 ml/min. We applied four analytic procedures to test the nature of AP and RBF time series, i.e., to determine if these variables are controlled randomly, if they consist of periodic oscillations, or whether they are best characterized as nonlinear dynamic processes. To this end, a fast Fourier transform was performed to quantify the amount of distinct periodic oscillations and nonperiodic variability in the very low frequency domain (< 0.01 Hz). The power spectrum of AP and RBF revealed broad band noise with no distinct peaks, which is commonly referred to as “1/f noise.” As a second procedure, time-delayed phase return maps were constructed, and as a third approach the correlation dimensions were estimated via the Grassberger-Procaccia algorithm. The correlation dimensions of RBF and AP were similar (RBF 3.3 +/- 0.37 vs. AP 3.6 +/- 0.23; P = 0.2). The fourth method determined sensitive dependence on initial conditions, a hallmark of nonlinear “chaotic” dynamics. We determined the maximal Lyapunov exponents and found them to be positive for AP (0.1 +/- 0.01) and for RBF (0.04 +/- 0.01) indicating that they both are nonlinear dynamic processes.(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship between cGMP and myocardial O2 consumption is altered in T4-induced cardiac hypertrophy
Authors: Weiss H. R. , Rodriguez E. , Tse J.
Published: December 2017

We tested the hypothesis that increases in guanosine 3',5'-cyclic monophosphate (cGMP) would reduce myocardial O2 consumption and that thyroxine (T4)-induced (0.5 mg/kg for 16 days) cardiac hypertrophy would change this relationship. Anesthetized open-chest New Zealand White rabbits were divided into four groups: control vehicle (CV, n = 7), control nitroprusside (CN, n = 6), T4 vehicle (T4V, n = 8), and T4 nitroprusside (T4N, n = 8). Vehicle or sodium nitroprusside (10(-4) M) was topically applied to the left ventricular subepicardium for 15 min. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption. Guanylate cyclase activity and cGMP were determined by radioimmunoassay. T4 increased the heart weight-to-body weight ratio from 2.7 +/- 0.1 to 3.4 +/- 0.2. Topical application of nitroprusside had no significant hemodynamic effects. Nitroprusside significantly increased myocardial cGMP in control hearts (CV = 4.1 +/- 0.3 to CN = 12.4 +/- 5.0 pmol/g) and T4 hearts (T4V = 3.9 +/- 0.3 to T4N = 5.2 +/- 0.4). The increase in the level of myocardial cGMP was significantly greater in CN (+202%) than in T4N (+33%). There were no significant differences in basal or total guanylate cyclase activity between control and T4 rabbits. Myocardial O2 consumption significantly declined in both groups during nitroprusside (10.8 +/- 1.4 for CV to 7.3 +/- 1.0 for CN (-32%) and 13.6 +/- 1.2 for T4V to 9.9 +/- 1.4 ml O2.min-1.100 g-1 for T4N (-27%).(ABSTRACT TRUNCATED AT 250 WORDS)