bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoproterenol induces release of atrial natriuretic peptide from rat atrium in vitro
Authors: Agnoletti G. , Rodella A. , Cornacchiari A. , Panzali A. F. , Harris P. , Ferrari R.
Published: December 2017

To investigate the mechanism underlying the release of atrial natriuretic peptide (ANP) in in vitro condition, isolated, superfused rat atria were subjected to adrenergic, chronotropic, and mechanical stimulation. First administration of isoproterenol (Iso; either 10(-9) or 10(-6) M) caused a release of ANP, which was transient. Subsequent increments in concentration of Iso always resulted in a much lower release of ANP, despite the increased effects on the mechanical function of the atria. Stretching of the atria resulted in a transient release of ANP. Subsequent increments in stretching were followed by decreasing release of ANP. The total score of ANP in atrial tissue after Iso and stretching was not measurably depleted. Pacing the atria with increasing frequency did not induce release of ANP. Depolarization with 40 mM KCl abolished the release of ANP in response to Iso but not the release induced by stretch. In the presence of low external Ca2+, which abolished mechanical activity, both Iso and stretch could still induce release of ANP. Propranolol abolished the release of ANP by Iso but not that induced by stretching. Prazosin did not affect the release by either stretch or Iso. Stretching the atria 20 min after administration of Iso did not cause any further release of ANP. On the other hand, adding Iso 20 min after stretching induced a release of ANP. It is concluded that Iso and stretch cause a transient release from isolated strips of atria. The amount of ANP released is not related to the dose of Iso or to the load applied. Mechanisms involved in the release mediated by the two stimuli are different.(ABSTRACT TRUNCATED AT 250 WORDS)
Onset of exercise shifts operating point of arterial baroreflex to higher pressures
Authors: DiCarlo S. E. , Bishop V. S.
Published: December 2017

This study was designed to test the hypothesis that the increase in sympathetic nerve activity (SNA) and mean arterial pressure (MAP) at the onset of exercise is dependent on a rapid upward shift of the operating point of the arterial baroreflex. To test this hypothesis, we recorded renal sympathetic nerve activity (RSNA) in 16 New Zealand White rabbits during treadmill running (12.6 m/min, 20% grade) under control conditions and during concomitant intravenous infusions of nitroglycerin (NTG) to attenuate the exercise pressor response. In the control condition, MAP increased 18 +/- 2 mmHg. This was associated with an increase in heart rate (HR) (104 +/- 4 beats/min) and RSNA (414 +/- 20%). The increases in RSNA (848 +/- 32%) and HR (155 +/- 5 beats/min) at the onset of exercise were significantly augmented when the rate of development of the exercise pressor response (0.3 +/- 0.03 to 0.12 +/- 0.01 mmHg/s) and the magnitudes of the pressor response (91 +/- 2 to 79 +/- 1 mmHg) were attenuated by infusions of NTG. These data suggest that at the onset of exercise the operating point of the arterial baroreflex is reset toward higher pressures. The MAP, RSNA, and HR responses to exercise were also determined in eight sinoaortic-denervated (SAD) rabbits. In the absence of a functional baroreflex, MAP (-46 +/- 2 mmHg), RSNA (-19 +/- 1%), and HR (-62 +/- 3 beats/min) decreased at the onset of exercise and recovered 1 min to -42 +/- 2, +13 +/- 1, and +9 +/- 1% of control, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence for two types of internal Ca2+ stores in canine mesenteric artery with different refilling mechanisms
Authors: Low A. M. , Kwan C. Y. , Daniel E. E.
Published: December 2017

Novel transient biphasic responses of the dog mesenteric artery to phenylephrine hydrochloride (PE, 10 microM) in Ca(2+)-free medium containing 50 microM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) have been analyzed. The initial component was significantly inhibited by ryanodine (30-100 microM), an agonist enhancing Ca2+ release from the sarcoplasmic reticulum, whereas the second was significantly inhibited by nifedipine (1 microM), and L-type Ca2+ channel antagonist, or EGTA, to chelate Ca2+, and was potentiated by BAY K 8644 (1 microM), an L-type Ca2+ channel agonist. After repletion of Ca2+ stores in normal Krebs solution or in high KCl (60 mM) Krebs, the first component was inhibited by cyclopiazonic acid (CPA, 30 microM), a putative, reversible, and selective microsomal Ca2+ pump adenosinetriphosphatase inhibitor. BAY K 8644 potentiated the second component in the presence of CPA. The inhibition of the first component by CPA suggests that the refilling ultimately requires the CPA-sensitive Ca2+ pump for Ca2+ resequestration. However, the second component may refill by a CPA-independent route opened by BAY K 8644. These results, taken as a whole, indicate that the biphasic PE response in Ca(2+)-free medium may reflect compartmentalization of Ca2+ storage related to the different routes of refilling.
Adrenal hormones interact with sympathetic innervation to modulate growth of embryonic heart in oculo
Authors: Tucker D. C. , Torres A.
Published: December 2017

To allow experimental manipulation of adrenal hormone and autonomic influences on developing myocardium without alteration of hemodynamic load, embryonic rat heart was cultured in the anterior eye chamber of an adult rat. Sympathetic innervation of embryonic day 12 heart grafts was manipulated by surgical sympathectomy of one eye chamber in each host rat. Adrenal hormone exposure was manipulated by host adrenal medullectomy (MEDX) in experiment 1 and by host adrenalectomy (ADX) in experiment 2. In experiment 1, whole heart grafts were larger in MEDX than in sham-operated hosts by 8 wk in oculo (6.14 +/- 0.71 vs. 5.09 +/- 0.69 mm2 with innervation intact and 7.97 +/- 2.07 vs. 3.09 +/- 0.63 mm2 with sympathetic innervation prevented). In experiment 2, host ADX increased growth of embryonic day 12 ventricles grafted into sympathectomized eye chambers (0.69 +/- 0.10 vs. 0.44 +/- 0.04 mm2) but did not affect growth of grafts in intact eye chambers (0.85 +/- 0.09 vs. 1.05 +/- 0.15 mm2). Corticosterone replacement (4 mg/day) entirely reversed the effect of host ADX on graft growth (superior cervical ganglionectomy, 0.47 +/- 0.03 mm2; intact eye chambers, 0.90 +/- 0.91 mm2). Beating rate of grafts was not affected by adrenal hormone manipulations. These experiments indicate that the compromised growth of embryonic heart grafts placed in sympathectomized eye chambers requires exposure to adult levels of glucocorticoids during the early days after grafting. These results suggest that interactions between neural and hormonal stimulation influence cardiac growth in the in oculo culture system and during normal development.
Disuse inhibition of newly functional coronary collateral circulation in ponies
Authors: Rugh K. S. , Ross C. R. , Sarazan R. D. , Boatwright R. B. , Williams D. O. , Garner H. E. , Griggs D. M.
Published: December 2017

We evaluated the loss of coronary collateral function in the absence of stimulation (disuse inhibition) by doubling the interval between successive left anterior descending coronary artery (LAD) occlusions in ponies in which collateral function initially had been enhanced by 2-min occlusions at 30-min intervals. Before collateralization, occlusion caused segment systolic shortening, velocity of shortening, and stroke work index in the LAD-dependent left ventricular apex to decrease, whereas heart rate and left ventricular end-diastolic pressure increased. After 476 +/- 102 occlusions, segment function recovered to preocclusion levels and hemodynamics were unchanged during occlusion. Occlusion did not elicit sustained functional deterioration until the occlusion interval was greater than or equal to 32 h. During the occlusion after the 128-h interval, segment systolic shortening, velocity of shortening, and stroke work index were reduced 69 +/- 8, 38 +/- 9, and 46 +/- 13%, respectively. Percent recovery of systolic shortening during successive occlusions declined exponentially (T1/e = 102.0 +/- 17.3 h). Thus, in ponies collateral function progressively declines when the occlusion interval is greater than or equal to 32 h, but complete inhibition does not occur even after 128 h without occlusion. This indicates that collateral function in ponies can be maintained by occlusions that are far less frequent than those needed for initial collateral development. The long time constant of collateral disuse inhibition suggests that equine collaterals are quite resistant to the effects of occlusion cessation and differ from canine collaterals in that respect.
Influence of saline infusions on transvascular protein transport
Authors: Gandhi R. R. , Bell D. R.
Published: December 2017

Anesthetized rabbits were given an intravenous infusion of saline over a 1-h period to increase transvascular protein transport in skin and skeletal muscle. The infusion rate was adjusted to rapidly decrease the plasma concentration of total protein without increasing mean arterial blood pressure or the venous pressure in the leg. The 1-h clearance for radiolabeled albumin and a set of charge-modified albumins was measured in the heel skin and the gastrocnemius muscle. For both skin and skeletal muscle, the clearance for native albumin during the saline infusion was twice the value for control. The increase in clearance for the most neutral protein was greater than that for native albumin, suggesting that transvascular fluid movement was through a pathway which excludes native albumin. The clearance for cationic albumin increased slightly in skin and did not change in skeletal muscle, indicating that transport of the cationic protein through this pathway is predominantly diffusion. The data were consistent with a two-pore model for transvascular transport of water and proteins and with the increase in water transport through the small pores during the saline infusion.
Is there a central nervous system component to acute baroreflex resetting in rats?
Authors: Heesch C. M. , Barron K. W.
Published: December 2017

This study was designed to evaluate a possible central nervous system (CNS) component to acute baroreflex resetting. In nine arterial baroreceptor-denervated, chloralose-urethan-anesthetized rats, a control (C) aortic nerve stimulation curve (3-5 V, 1 ms, 0-64 Hz) was obtained. Next, a constant "baroreceptor" input was delivered to the CNS (left aortic nerve stimulation, 10 min, 10.2 +/- 1.5 Hz). Within the first 13 s of aortic nerve stimulation, maximum inhibition of lumbar sympathetic nerve activity (LSNA) was 60 +/- 7.8% of baseline and at 1 min it increased to 68 +/- 5.6% of baseline. At the end of the 10-min aortic nerve stimulation, LSNA was not different from the response at 1 min (68 +/- 5.6% = 74 +/- 4.1%). Immediately after the constant stimulation (within 30 s), a test or reset (RS) curve was obtained (0-64 Hz). A recovery (RC) curve was obtained 10-20 min later. The slope of the linear portion of the curve and the stimulation frequency that produced 50% maximum inhibition (ES50) were compared among the three baroreflex curves (C, RS, RC,) and no significant differences were found. Thus, although a CNS component to baroreflex adaptation was evident during the first minute of aortic nerve stimulation, a longer term acute resetting of the baroreflex curve did not occur.
Comparison of hypoxia-induced contraction in human, monkey, and dog coronary arteries
Authors: Toda N. , Matsumoto T. , Yoshida K.
Published: December 2017

In monkey coronary artery strips contracted with prostaglandin (PG) F2 alpha or K+, exchange of entire N2 for O2 in the gas aerating the bathing media produced a contraction. Endothelium denudation did not alter the response. Aspirin, indomethacin, and ONO 3708, a PG receptor antagonist, markedly inhibited the hypoxia-induced contraction, whereas superoxide dismutase and OKY 046, a thromboxane (Tx) A2 synthesis inhibitor, were ineffective. Diltiazem depressed the contraction. Hypoxia increased the release of PGE2 but not 6-keto-PGF1 alpha and TxB2. Contractions induced by hypoxia of human coronary artery strips were also independent of the endothelium but were suppressed by indomethacin and diltiazem. On the other hand, dog coronary artery contractions induced by hypoxia were attenuated by endothelium denudation but were not influenced by indomethacin. It may be concluded that the hypoxia-induced contraction of monkey and human epicardial coronary arteries is associated with vasoconstrictor PGs released from subendothelial tissues; however, TxA2 and superoxide anion are not involved. The dog coronary artery contraction appears to be elicited by substance(s), other than cyclooxygenase products, released from the endothelium.
Systemic and regional O2 delivery and uptake in bled dogs given hypertonic saline, whole blood, or dextran
Authors: Curtis S. E. , Cain S. M.
Published: December 2017

The mechanisms by which small volumes of hypertonic saline in dextran (HSD) resuscitate bled dogs are incompletely understood but may include a pulmonary osmolar reflex. A known negative effect of HSD is hemodilution that reduces O2-carrying capacity. Our goals in this study were to ascertain whether the putative osmotic reflex redistributed blood flow between muscle and gut and whether O2 delivery (DO2) was adequate at systemic and regional levels. Left hindlimb muscle and a segment of ileum were vascularly isolated in three groups (n = 8) of anesthetized dogs that were then bled to mean arterial pressure (MAP) of 40 mmHg for 30 min. At that point, all shed blood (approximately 40 ml/kg) was returned in the blood group (BLD); 20 ml/kg of Dextran 70 was given to the dextran group (DEX); and 5 ml/kg of 7.5% NaCl in dextran was given to the HSD group. MAP and cardiac output were restored to acceptable levels in all but was poorly maintained in HSD. The fall in hematocrit (41 to 25%) in HSD was matched by that in DEX (42 to 22%), so that DO2 only reached approximately 55% of that in BLD. Nevertheless, systemic and regional O2 uptakes were similar; O2 debt and repayment did not differ; and lactate metabolism was alike in all groups. O2 extraction did have to increase to near maximum in HSD, however. Other than a transient increase to muscle, HSD had no special effect on distribution of cardiac output. HSD was efficacious as a short-term resuscitative measure but did encroach markedly on O2 transport reserves.
Responses of cerebral arterioles during chronic ethanol exposure
Authors: Mayhan W. G.
Published: December 2017

The purpose of this study was to examine the effects of ethanol exposure on responses of cerebral arterioles in vivo. Rats were fed liquid diets with or without ethanol for 2-3 mo. Using intravital microscopy, we measured diameter of cerebral arterioles in non-ethanol- and ethanol-fed rats in response to acetylcholine, histamine, ADP, the thromboxane analogue (U-46619), and nitroglycerin. In non-ethanol-fed rats, acetylcholine, histamine, and ADP produced dose-related dilatation of cerebral arterioles. In ethanol-fed rats, however, acetylcholine produced vasoconstriction, and vasodilatation in response to histamine and ADP was impaired. Dilatation of cerebral arterioles in response to nitroglycerin and vasoconstriction in response to the thromboxane analogue (U-46619) were similar in non-ethanol-fed and ethanol-fed rats. Thus these findings suggest that chronic ethanol exposure impairs responses of cerebral arterioles to agonists, which produce dilatation via the release of an endothelium-derived relaxing factor. We speculate that impaired vasodilatation coupled with preservation of vasoconstriction in ethanol-fed rats may have important implications for the pathogenesis of stroke during chronic alcohol ingestion.
Dynamic interaction of vagal activity and heart rate on atrioventricular conduction
Authors: Wallick D. W. , Xu R. G. , Martin P. J.
Published: December 2017

The dynamic effects of 1) brief bursts of vagal stimuli and 2) changing heart periods (A-A interval) on the atrioventricular conduction time (AVCT) were studied in open-chest, anesthetized (pentobarbital, 30 mg/kg) dogs (n = 8) under beta-adrenergic blockade (propranolol, 1 mg/kg). Four different atrial and/or vagal stimulation paradigms were used to quantitate the interactions between these two separate effects. We measured the AVCT responses to identical vagal stimuli both when the heart was paced and when it was not paced. When the heart was not paced, we collected and stored in computer memory the sequences of dynamically changing heart periods that followed each vagal stimulus burst. Later, without vagal stimuli, we played these sequences of changing intervals back into the atrial pacing electrodes and measured the subsequent AVCT responses to those changes of heart period alone in the absence of vagal activity. We also measured the AVCT responses when we played these intervals back into the atrial pacing electrodes but when identical vagal stimuli were simultaneously applied, so as to absolutely fix the site of atrial activation. We found that these two separate effects of vagal stimuli and changing A-A intervals on AVCT were not linearly additive. For example, the response of the atrioventricular (AV) node to the two combined effects was less than the linear sum of the AV response to the two separate perturbations. Our results further suggest strongly that shifts in the pacemaker site may not be an important mechanism for the paradoxical response of the AV node to vagal stimulation under the present experimental conditions.
Differential changes in left and right ventricular SR calcium transport in congestive heart failure
Authors: Afzal N. , Dhalla N. S.
Published: December 2017

To examine the status of sarcoplasmic reticulum (SR) with respect to Ca2+ transport in congestive heart failure due to myocardial infarction, the left coronary artery in rats was ligated for 4, 8, and 16 wk. The left heart function was assessed with an intraventricular pressure transducer, and SR membrane fractions from the right ventricle and the viable left ventricle were isolated for measuring the ATP-dependent Ca2+ uptake activities. In comparison to sham-operated controls, SR Ca2+ uptake activity was decreased in viable left ventricle of the experimental animals at 4, 8, and 16 wk. On the other hand, SR Ca2+ uptake activity in the right ventricle was increased at 4 and 8 wk, but no change was apparent at 16 wk of coronary occlusion. The decrease in SR Ca2+ uptake in left ventricle and increase in right ventricle were associated with corresponding changes in maximal velocity values without any alterations in the affinity for Ca2+. These opposite changes in the right and left ventricles were dependent on the scar size as well as time after inducing the myocardial infarction. The SR Ca(2+)-stimulated adenosinetriphosphatase activity was decreased in left ventricle and increased in the right ventricle from 4 wk experimental animals. The results suggest differential remodeling of the SR membranes with respect to Ca(2+)-pump mechanisms in left and right ventricles during the development of congestive heart failure.
Delayed rectification in single cells isolated from guinea pig sinoatrial node
Authors: Anumonwo J. M. , Freeman L. C. , Kwok W. M. , Kass R. S.
Published: December 2017

We have studied delayed rectifier K+ currents (IK) in cells isolated from the sinoatrial node (SAN) region of the guinea pig. Using whole cell patch-clamp procedures, we measured the voltage dependence of IK activation and IK kinetics and the IK equilibrium potential in 4.8 mM extracellular K concentration solutions. Experiments were designed to contrast properties of guinea pig SAN IK with those of IK recorded from SAN cells of the rabbit. We find that guinea pig SAN IK differs from IK recorded from single rabbit SAN cells in its activation threshold, and in the absence of inactivation of whole cell currents recorded over a wide voltage range. These results, along with the relative insensitivity of guinea pig SAN IK to E-4031 and lanthanum, suggest that under our experimental conditions, a strongly rectifying IK component (IK,r) is not the major component of delayed rectification in the guinea pig SAN, as it appears to be in SAN cells of the rabbit.
Plasma volume expansion with colloids increases blood-tissue albumin transport
Authors: Renkin E. M. , Tucker V. , Rew K. , O'Loughlin D. , Wong M. , Sibley L.
Published: December 2017

Extravasation of plasma proteins is increased after volume expansion with whole blood or plasma. To investigate the mechanisms responsible for this phenomenon, we measured extravascular accumulation of exogenous 131I-labeled bovine serum albumin in several tissues and organs of anesthetized rats. Plasma volume was increased acutely by infusion of isoncotic albumin or polyvinylpyrrolidone, with or without subsequent infusion of a 1:10 dilution of the colloid to induce blood-to-tissue fluid movement. Controls were given only a slow sustaining infusion of saline. The amounts of fluid and plasma protein lost from the circulation were followed simultaneously by two methods: 1) material balance in the whole animal, and 2) changes in 131I-labeled albumin uptake (VA) and water content (VW) in the individual tissues. Plasma volume expansion of 80-90% increased plasma protein extravasation in the whole rat by an average of 2.7-fold over a 30-min period. Of the protein extravasated, 42% entered the abdominal cavity. The rest was distributed in the interstitial compartment of various tissues and organs. Tracer albumin accumulation (averaged over 30 min) was increased 38-82% in skin and paw, 40-59% in skeletal muscles, 131% in hearts, and 167-230% in different parts of the intestine. Increased convective transport does not appear to be a major factor. There was little or no relation of albumin transport increase to the magnitude or direction of net fluid transfer. Coupling of albumin transport to volume flow was not greater than previously reported for saline infusion or venous congestion. Convective redistribution (convective transport without net fluid transfer, “volume recirculation”) is estimated to increase albumin transport no more than 10% under the conditions of our experiments. The greater part of the increase is thus dissipative, i.e., attributable to increased diffusion or increased vesicular exchange. Control of dissipative transport of albumin may play an important role in regulating plasma volume.
Transient venular permeability increase and endothelial gap formation induced by histamine
Authors: Wu N. Z. , Baldwin A. L.
Published: December 2017

Histamine is known to increase permeability of venules and to cause formation of gaps between endothelial cells. The permeability increase is transient, lasting only a few minutes during continuous histamine application. In this study, three series of experiments were conducted to test the hypothesis that the transient permeability increase is due to transient formation of endothelial gaps. First, the time course of permeability changes to alpha-lactalbumin during 15 min of 10(-3) M histamine suffusion was determined on single venules in the rat mesentery. With histamine application, permeability increased initially, peaked with an average of fivefold increase around the 3rd min, and then declined toward control. Second, the temporal development of endothelial gaps during histamine treatment was studied with electron microscopy. The fraction of gaps among all junctions increased from 2% at control to 26.5% at 3 min and then decreased toward control. Finally, gap morphology data were obtained from the individual venules whose permeability response to a given period of histamine treatment had been recorded. The temporal development of the gaps was mirrored by that of permeability. Because both permeability and endothelial gaps followed similar developmental patterns during histamine treatment, the result of our study supports the hypothesis that the histamine-induced transient permeability increase is due to transient formation of endothelial gaps.
Arteriolar endothelial cell barrier separates two populations of muscarinic receptors
Authors: Rivers R. J. , Duling B. R.
Published: December 2017

The endothelium of arterioles can function as a barrier to diffusion of hydrophilic molecules when studied in vitro. Thus a substance applied to one side of the arteriole is relatively ineffective in reaching receptors on the opposite side of the vessel wall unless it is lipid soluble. To study the receptor populations on the two sides of the arteriolar endothelium, we used micropipettes to apply methacholine (MCh; 1.0 microM), either luminally or adventitially, for 5 s to the arterioles of the cheek pouch of pentobarbital-anesthetized hamsters. MCh equally dilated the arterioles regardless of the side of application. That different populations of receptors are located on either side of the arteriole was shown by the fact that adventitially applied hydrophilic methscopolamine was ineffective in blocking the effects of the luminally applied MCh but completely blocked the effects of abluminally applied MCh. In contrast, the luminal population of receptors was easily blocked by adventially applied scopolamine, which is lipophilic. Separate and independent populations of receptors in the vessel wall suggests the potential for differential control between humoral and adventitial sources of vasoactive metabolites.
Effects of a coronary alpha 1-constriction on transmural left ventricular flow and contractile function
Authors: Gwirtz P. A. , Dodd-O J. M. , Downey H. F. , Mass H. J. , Barron B. A. , Williams A. G. , Jones C. E.
Published: December 2017

Modulation of myocardial contractile function and perfusion by alpha 1-adrenergic receptors were examined in anesthetized dogs during left stellate ganglion stimulation. In 11 dogs, stellate stimulation significantly increased heart rate, mean arterial pressure, left ventricular systolic pressure, maximal rate of left ventricular pressure generation, segmental shortening and rate of shortening in anterior and posterior ventricular regions, and myocardial oxygen extraction. Myocardial lactate extraction decreased. The selective alpha 1-adrenergic antagonist prazosin (0.5 mg) injected into the circumflex artery during stellate stimulation caused significant additional increases in maximal rate of left ventricular pressure generation by 19 +/- 5% and in rate of shortening in posterior subendocardium by 20 +/- 6%. No changes were observed in posterior subepicardial or anterior subendocardial segmental contractile function. Myocardial oxygen and lactate extractions returned to their control values following prazosin injection. Regional left ventricular perfusion was measured using tracer microspheres in five additional dogs. Stellate stimulation increased subepicardial and subendocardial perfusion by 30%. Prazosin increased both subepicardial and subendocardial perfusion by an additional 36%. Stellate stimulation increased norepinephrine concentration in the coronary sinus, but no further increase was noted after blockage of alpha 1-receptors by prazosin. Thus, during sympathetic stimulation, an alpha 1-vasoconstriction existed uniformly across the left ventricular wall. However, blockade of this vasoconstriction was associated with an increase in contractile function only in the deeper muscle layers.
Passive effect of reduced cardiac function on splanchnic intravascular volume
Authors: Rutlen D. L. , Welt F. G. , Ilebekk A.
Published: December 2017

It has been hypothesized that lowered cardiac output due to heart failure results in passive redistribution of intravascular volume from the peripheral circulation to the central circulation and that this redistribution acts to support cardiac output. To test this hypothesis, acute heart failure was induced by rapid atrial pacing to raise heart rate from 148 +/- 6 to 232 +/- 1 beats/min for 5 min, while splanchnic intravascular volume was assessed with radionuclide imaging in eight anesthetized pigs that had undergone prior carotid denervation and vagotomy. Cardiac output decreased from 3,350 +/- 410 to 2,170 +/- 290 ml/min (P less than 0.001), mean arterial pressure decreased from 103 +/- 5 to 84 +/- 4 mmHg (P less than 0.001), left atrial pressure increased from 5.9 +/- 0.6 to 10.8 +/- 0.9 mmHg (P less than 0.001), right atrial pressure increased from 2.4 +/- 0.5 to 4.8 +/- 0.9 mmHg (P less than 0.001), total splanchnic intravascular volume did not change (0 +/- 2 ml), splenic intravascular volume decreased 11 +/- 3% (P less than 0.001), hepatic intravascular volume increased 12 +/- 2% (P less than 0.001), and mesenteric intravascular volume did not change (-3 +/- 2%). Thus, when cardiac output is lowered with pacing-induced acute heart failure, lowered perfusion pressure acts to lower splenic intravascular volume and increased central venous pressure acts to increase hepatic intravascular volume; however, total splanchnic intravascular volume does not decrease to support cardiac filling and cardiac output.
Effect of dietary n-3 fatty acids on cerebral microcirculation
Authors: Ellis E. F. , Police R. J. , Dodson L. Y. , McKinney J. S. , Holt S. A.
Published: December 2017

The purpose of these studies was to determine the effects of dietary n-3 fish oil on cerebrovascular reactivity and cerebrospinal fluid prostaglandin levels. Adult rabbits (n = 30) received fish oil (200 mg/kg eicosapentaenoic + 143 mg/kg docosahexaenoic acid), corn oil, or water by daily gavage for 6 wk and were then tested for their pial arteriolar diameter response to topical acetylcholine, bradykinin, or systemic asphyxia using the cranial window technique. Plasma and platelet fatty acids were measured by gas chromatography. Cerebrospinal fluid prostaglandin E and serum thromboxane B2 were measured by radioimmunoassay. n-3 Fatty acids were enriched in the plasma and platelets of the fish oil group (P less than 0.05). Serum thromboxane B2 was decreased by 31% in the fish oil group (P less than 0.05). The diameter response to acetylcholine and asphyxia was the same in all groups; however, the dilator response to bradykinin, which is known to be mediated by oxygen radicals, was significantly diminished in the fish oil group (P less than 0.05). Cerebrospinal fluid prostaglandin E concentration increased in response to acetylcholine, bradykinin, and asphyxia; however, the percent increase was less in the fish oil group. In summary, dietary n-3 fatty acids, which are purported to decrease heart disease, appear to selectively affect cerebral arteriolar reactivity, which is normally dependent on cyclooxygenase metabolism of arachidonic acid and formation of vasoactive oxygen radicals.
Phasic characteristics of arterial inflow and venous outflow of right ventricular myocardium in dogs
Authors: Hiramatsu O. , Kimura A. , Yada T. , Yamamoto T. , Ogasawara Y. , Goto M. , Tsujioka K. , Kajiya F.
Published: December 2017

To clarify the characteristics and causes of phasic blood flow in coronary circulation of the right ventricle we measured blood velocities in peripheral portions of the right coronary artery and vein in dogs under three conditions: control, transient pulmonary stenosis, and isoproterenol administration. An optical fiber sensor of a laser Doppler velocimeter was fixed onto the vessels (150-500 microns OD) with cyanoacrylate. The phasic pattern of distal arterial velocity was compared with the proximal velocity in the right coronary artery measured with an ultrasound pulsed Doppler velocimeter. Systolic-to-total velocity area ratio in the small epicardial artery [0.38 +/- 0.03 (SE)] was found to be smaller than in the large epicardial artery (0.51 +/- 0.02, P less than 0.01), indicating a capacitive filling of the epicardial artery during systole. The velocity waveform in small right coronary veins was predominantly systolic; i.e., it increased with a rise of right ventricular pressure and decreased with right ventricular relaxation. Comparison of the waveforms during isoproterenol infusion and pulmonary stenosis indicates that contraction of the ventricle is more important than right ventricular systolic pressure in retarding arterial inflow and accelerating venous outflow.
Differential recovery of prostacyclin and endothelium-derived relaxing factor after vascular injury
Authors: Saroyan R. M. , Roberts M. P. , Light J. T. , Chen I. L. , Vaccarella M. Y. , Bang D. J. , Kvamme P. , Singh S. , Scalia S. V. , Kerstein M. D. , et al.
Published: December 2017

Differential recovery of prostacyclin and endothelium-derived relaxing factor after vascular injury. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1449-H1457, 1992. The recovery of prostacyclin (prostaglandin I2, PGI2) synthesis and endothelium-derived relaxing factor (EDRF) activity, as demonstrated by acetylcholine (ACh)-induced relaxation, by rabbit aorta was examined up to 8 wk after balloon catheter-induced injury. Following injury, basal 6-keto-PGF1 alpha formation was decreased acutely; however, after 3 wk it was not different from control. Arachidonic acid-stimulated 6-keto-PGF1 alpha formation was decreased, returning to control levels at 3 and 8 wk for thoracic and abdominal aorta, respectively. ACh-induced relaxation did not return to control levels over the 8-wk study. Initiation of reendothelialization with a layer of hyperplastic endothelial cells overlying subendothelial fibrosis and intimal hyperplasia were present at 2-3 wk. Intimal hyperplasia appeared 2 wk after injury and progressed throughout the period of the study. These data indicate that following balloon catheter-induced injury the formation of both PGI2 and EDRF is reduced and that recovery follows a differential time course. In addition, the recovery of PGI2 formation did not coincide with the attenuation of intimal hyperplasia, whereas the relationship between EDRF formation and intimal hyperplasia is uncertain.
Role of endogenous ANP in sodium excretion in rats with experimental pulmonary hypertension
Authors: Hirata Y. , Suzuki E. , Hayakawa H. , Matsuoka H. , Sugimoto T. , Kojima M. , Kangawa K. , Matsuo H.
Published: December 2017

To explore the roles of endogenous atrial natriuretic peptide (ANP) in the volume regulation, we examined effects of antiserum for ANP or a neutral endopeptidase inhibitor, thiorphan, in rats with monocrotaline (MCT)-induced pulmonary hypertension. ANP concentrations in the plasma and right ventricle and ANP mRNA in the right ventricle of MCT-treated rats were higher than in vehicle-treated rats. The administration of the ANP antiserum into the MCT-treated rats did not affect the right atrial pressure or blood pressure but significantly decreased urinary excretion of Na by 60%. No decrease occurred in the control rats. Thiorphan dose dependently increased the urinary excretion of Na by 140% without influencing the right atrial pressure or blood pressure. This natriuresis was associated with 50 and 450% increases in ANP concentrations in the plasma and urine, respectively. The degrees of increases in urinary Na excretion, ANP, and guanosine 3',5'-cyclic monophosphate were significantly greater in the MCT-treated rats than in the control rats. Thus an increased secretion of ANP in pulmonary hypertension actually contributes to Na excretion. The augmentation of endogenous ANP activity may further potentiate the compensatory role of this peptide in the regulation of body fluid volume.
Restraining effect of intact pericardium during acute volume loading
Authors: Applegate R. J. , Johnston W. E. , Vinten-Johansen J. , Klopfenstein H. S. , Little W. C.
Published: December 2017

To determine the effect of the intact pericardium on ventricular end-diastolic pressures (EDP) during acute volume loading, we measured left ventricular (LV) and right ventricular (RV) micromanometer pressure and LV volume using a conductance catheter in eight open-chest, anesthetized dogs. A range of LV pressure and volume was obtained by intravascular volume expansion with the pericardium intact and then over a similar range after removal of the pericardium. Pericardial pressure (Pper) was calculated using static equilibrium analysis as the difference between LVEDP with the pericardium present and absent at a constant LV volume. At the beginning of the fluid infusion (LVEDP 7.3 +/- 1.7 mmHg and RVEDP 4.4 +/- 2.6 mmHg, mean +/- SD), Pper was not different from zero (-1.0 +/- 2.3 mmHg, P not significant). The onset of pericardial restraint (Pper greater than or equal to 0 mmHg) occurred when LVEDP was 9.1 +/- 2.9 mmHg and RVEDP was 4.1 +/- 2.9 mmHg. At low cardiac volumes before fluid infusion, RV transmural pressure was positive and significantly greater than the near zero Pper. After the onset of pericardial restraint, however, RVEDP and Pper increased similarly and were related according to Pper = 1.1 (+/- 0.34) RVEDP - 4.2 (+/- 2.6) mmHg, standard deviation 0.6 +/- 0.8 mmHg, r = 0.98 +/- 0.10. These data indicate that the intact pericardium behaves in two functionally distinct ways. At low cardiac volumes, Pper is zero and the pericardium does not affect LV filling. RV transmural pressure is positive and greater than Pper.(ABSTRACT TRUNCATED AT 250 WORDS)
Does systolic subepicardial perfusion come from retrograde subendocardial flow?
Authors: Flynn A. E. , Coggins D. L. , Goto M. , Aldea G. S. , Austin R. E. , Doucette J. W. , Husseini W. , Hoffman J. I.
Published: December 2017

To examine the influence of cardiac contraction on systolic coronary flow and transmural blood flow distribution, we measured phasic blood flow velocity in distal extramural coronary arteries by Doppler velocimeter and regional myocardial blood flow by radiolabeled microspheres while the heart was beating and during prolonged diastoles in 12 dogs. A servo-controlled coronary perfusion circuit allowed mean coronary pressure to be selected and maintained during beating and diastolic conditions. In epicardial arteries just proximal to their entrance into the myocardium, blood flow was either negligible or reverse in direction during systole. When the heart was beating, subepicardial blood flow was 24.2 +/- 12.3% higher than during asystole (5.05 +/- 0.91 and 4.11 +/- 0.79 ml.min-1.g-1 for beating and prolonged diastoles, respectively; P less than 0.01). In the subendocardium, flow was 49.8 +/- 14.7% lower in the beating condition than during prolonged diastoles (4.23 +/- 1.46 and 8.26 +/- 1.71 ml.min-1.g-1 for beating and asystole, respectively; P less than 0.01). When heart rate was increased stepwise from 60 to 150 beats/min, subendocardial flow fell approximately linearly; flow to the superficial layer was relatively unaffected. In beating hearts, lowering mean left main coronary artery (LMCA) pressure from 80 to 50 mmHg resulted in more systolic reverse flow and a fall in inner-to-outer flow ratio from 0.82 +/- 0.18 to 0.66 +/- 0.34 (P less than 0.05). Because mean LMCA pressure was held constant when the heart was stopped, differences in regional blood flow between beating and diastolic conditions were primarily due to cardiac contraction. Because little or no blood entered the myocardium from the extramural arteries during systole, we conclude that the decrease in subendocardial flow and the increase in subepicardial flow were caused by retrograde pumping of blood from the deep layer to the superficial layer of the left ventricle. Systolic retrograde flow to the subepicardium may help explain this layer's relative protection from ischemia.
Kidney cross transplants in Dahl salt-sensitive and salt-resistant rats
Authors: Churchill P. C. , Churchill M. C. , Bidani A. K.
Published: December 2017

Previous kidney cross-transplant studies have demonstrated that the genotype of the kidney plays a role in determining the blood pressure of the recipient in Dahl salt-sensitive (S) and salt-resistant (R) rats. The present studies were designed to elucidate this role. Kidney cross transplants were performed in unilaterally nephrectomized male recipients (John Rapp strains), such that each rat had a native kidney and a transplanted kidney of the opposite genotype. S and R rats with a native kidney and a transplanted kidney of the same genotype served as controls. After 4 wk on a 7.8% NaCl diet, rats were anesthetized and renal clearance studies were performed. S kidneys had lower glomerular filtration rate (GFR) and renal plasma flow (RPF) than R kidneys, and these differences were determined by the kidney's genotype rather than the recipient's, since S kidneys in R recipients tended to have lower GFR and RPF than R kidneys in S recipients. In contrast, independent of the kidney's genotype, the kidneys in S rats tended to have higher fractional excretion of H2O and Na (FEH2O and FENa) than the kidneys in R rats. Thus there were genetically determined differences in renal function between S and R rats; some (RPF and GFR) were intrinsic to the kidney, whereas others (FEH2O and FENa) were intrinsic to the host.(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction of lysophosphatidylcholine with aortic endothelial cells
Authors: Stoll L. L. , Oskarsson H. J. , Spector A. A.
Published: December 2017

To better understand the vascular actions of lysophosphatidylcholine (lysoPC), we studied the interaction of [1-14C]palmitate-labeled lysoPC with bovine aortic endothelial cells. These cells took up lysoPC from media containing albumin, low-density lipoproteins (LDL), or acetyl-LDL. Uptake occurred faster than conversion to phosphatidylcholine (PC), leading to some lysoPC accumulation in endothelial lipids. Endothelial cell monolayers grown on micropore filters took up lysoPC from both apical and basolateral surfaces, preventing substantial amounts from passage across the endothelial monolayer. However, lysoPC present in the interstitial medium of an endothelial-smooth muscle coculture was incorporated primarily by the smooth muscle cells. Endothelial cells grown on filters released lysoPC into both the apical and basolateral medium in the presence of albumin or lipoproteins. Exposure to 50 microM lysoPC produced no evidence of endothelial cytotoxicity, but prostaglandin (PG)I2 production was reduced. These studies suggest that the endothelium can participate in the processing of circulating lysoPC and, through basolateral uptake, can facilitate the removal of lysoPC formed within the arterial wall. By decreasing PGI2 output, however, exposure to high concentrations of lysoPC may reduce the antithrombotic and vasodilator capacity of the endothelium.
An animal model of chronic coronary stenosis resulting in hibernating myocardium
Authors: Bolukoglu H. , Liedtke A. J. , Nellis S. H. , Eggleston A. M. , Subramanian R. , Renstrom B.
Published: December 2017

An experimental animal model of hibernating myocardium is presented. Sixteen animals were initially prepared of which seven were selected for final review. Hearts were instrumented in two separate surgical procedures such that maximum phasic flow velocity in the left anterior descending (LAD) coronary artery was reduced by 50% and followed over 1 wk. Regional shortening declined at 1 wk to 62% of aerobic values (P less than 0.048) and did not improve over 2 h reperfusion. Metabolic determinations, obtained after 1 wk of coronary stenosis and immediately sampled before and after release of the LAD flow constrictor, showed no evidence of acidosis, hypercarbia, or an inability to extract oxygen at the tissue level. Thereafter, during the 2-h reperfusion period, hearts were able to respond to dobutamine (10 micrograms/kg infusion over 1 min) challenge with an appropriate shift in an end-systolic length estimate of contractility. Mitochondrial respiration at the conclusion of the studies in the reperfused bed demonstrated near normal recovery compared with aerobic values. None of the seven hearts showed gross evidence of infarction and only one heart was noted to have a few microfocal changes of healing infarction. Thus a new model of coronary stenosis is presented, which affected substantial reductions in mechanical function consistent with the concepts of hibernating myocardium. These mechanical events were not associated with marked metabolic abnormalities, reflecting advanced ischemia or mitochondrial dysfunction and could be transiently improved with inotropic stimuli. This model may prove beneficial as a tool in understanding mechanistic events underlying the hibernating heart.
Entry rate and metabolism of leukotriene C4 into vascular compartment in healthy subjects
Authors: Maclouf J. , Antoine C. , De Caterina R. , Sicari R. , Murphy R. C. , Patrignani P. , Loizzo S. , Patrono C.
Published: December 2017

We measured the excretion of a major urinary metabolite of leukotriene (LT) C4, i.e., LTE4, during the infusion of exogenous LTC4 to enable estimation of the rate of entry of endogenous LTC4 into the bloodstream. Four healthy volunteers received 2-h intravenous infusions of vehicle alone and LTC4 at 0.063, 0.32, 1.6, and 2.9 pmol.kg-1.min-1 in random order. Urinary LTE4 was measured before, during, and up to 24 h after the infusions. The fractional elimination of LTE4 was independent of the rate of LTC4 infusion and averaged 4.3 +/- 0.9%. Calculation of the mean rate of entry of LTC4 into the circulation was found to be 0.06 pmol.kg-1.min-1. In addition, we characterized further metabolism of [14C]LTC4. The two major urinary metabolites were the omega- and beta-oxidation products (16-COOH-LTE4 and 14-COOH-LTE3), which accounted for 6-8% of the total infused amount of [14C]LTC4. We conclude that 1) LTC4 is produced at a low rate under physiological circumstances and is rapidly converted in the vasculature to LTE4, 2) changes in the urinary excretion of the latter may reliably reflect short-term changes in the rate of secretion of LTC4, and 3) measurement of the omega- and beta-oxidation products may reflect chronic changes in cysteinyl leukotriene biosynthesis.
Altered agonist-induced Ca2+ mobilization in aortic smooth muscle cells from cardiomyopathic hamsters
Authors: Tawada-Iwata Y. , Furukawa K. , Ogurusu T. , Nakamura H. , Shigekawa M.
Published: December 2017

We compared the responses to the Ca(2+)-mobilizing effects of norepinephrine (NE), endothelin-1 (ET), and arginine vasopressin (AVP) of primary cultures of vascular smooth muscle cells (VSMCs) from aortas of young (30-40 days old) cardiomyopathic (Bio 14.6 strain) and age-matched control hamsters. In Bio 14.6 VSMCs, saturating concentrations of NE and ET elicited increases in the intracellular Ca2+ concentration ([Ca2+]i), which reached approximately 50 and 62% of those in control VSMCs. AVP elicited a significant increase in [Ca2+]i only in Bio 14.6 VSMCs. In contrast, 10 microM ionomycin induced similar Ca2+ responses in both types of cells in the absence of extracellular Ca2+. Ligand binding assay revealed that maximal binding values for alpha 1-adrenergic antagonists and ET in Bio 14.6 VSMCs were 59-64 and 85% of those in control VSMCs. Thus VSMCs from aortas of Bio 14.6 hamsters had reduced reactivity to NE and ET but increased response to AVP. The reduced Ca2+ response of Bio 14.6 VSMCs to NE appeared to be due mainly to a decrease in the receptor number.