bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of adrenergic responses in pressurized resistance arteries by flow
Authors: Tesfamariam B. , Halpern W.
Published: December 2017

The effects of perfusion on the reactivity of isolated rat resistance mesenteric arteries (200 micron ID) to electrical stimulation and exogenous norepinephrine (NE) were investigated. Diameter constrictions of these arteries that have an intact endothelium in response to the stimuli were significantly greater (P less than 0.05) in the presence than in the absence of flow. Inhibition of NE uptake and metabolism with cocaine, normetanephrine, and pargyline increased constrictor responses to electrical stimulation and NE in the presence and absence of flow, but responses remained larger in the presence of flow. Endothelial cell removal augmented the NE-induced diameter constrictions, which were not different whether or not flow was present. Perfusion at similar flows but a higher shear stress using a dextran solution led to smaller constrictions than obtained at lower shear stress in response to NE. However, NE-induced constrictions at high and low shear stresses were the same after endothelium removal. These observations suggest that NE and elevated levels of shear stress induce the release of relaxing factors from the endothelium, which attenuates direct NE smooth muscle cell constrictor responses.
Force-length dependence of arterial lamellar, smooth muscle, and myofilament orientations
Authors: Walmsley J. G. , Murphy R. A.
Published: December 2017

Force generation by contractile elements of arterial tissue can be affected by alterations in their alignment with shortening. The orientation and morphometry of smooth muscle (SM) myofilaments, medial lamellae, and elastic laminae were examined as a function of length in intact swine carotid arteries or strips. Intimal-medial tissue strips were fixed during isometric contractions at lengths (L) defined with respect to the optimal length for force generation (Lo). The average orientation of SM cells in two perpendicular planes remained parallel to the long axis of the tissue at all lengths, but the absolute value of angular deviations increased with shortening. Tissue lengthening was associated with decreased folding of the elastic laminae. This decrease in waviness was quantified by a stretch index (SI). Ultrastructural observations indicated that the myofilament absolute angular deviation was greater than that for the cellular alignment. For arteries fixed in situ while constricted, SI was least in the periintimal laminae and increased in the peripheral laminae. The average decrease in force-generating capacity on shortening from Lo to 0.6 Lo attributed to increasing SM and myofilament angular deviations was calculated to be 7%.
Neural, hemodynamic, and renal responses to stimulation of intestinal receptors
Authors: Weaver L. C. , Genovesi S. , Stella A. , Zanchetti A.
Published: December 2017

Stimulation of visceral receptors with bradykinin has been shown to cause reflex increases in sympathetic nerve activity and systemic arterial pressure. In this investigation, serosal receptors of the intestine were stimulated by bradykinin in anesthetized cats to 1) compare mesenteric and renal sympathetic responses, 2) compare hemodynamic responses in mesenteric and renal beds, and 3) determine changes in renal function. This stimulation in intact animals caused pressor responses, significantly greater excitation of mesenteric than renal nerves, significantly greater mesenteric than renal vasoconstriction, diuresis, natriuresis, and, in denervated kidneys, increases in fractional sodium excretion. In vagotomized, sinoaortic-denervated cats, stimulation of intestinal receptors caused excitation of mesenteric nerve activity greater than renal for only 30 s. This sympathetic reflex response led to pressor responses, equal mesenteric and renal vasoconstriction, diuresis, natriuresis, and increased fractional excretion of sodium only in denervated kidneys. When abdominal perfusion pressure was held constant with an aortic snare in these same animals, the sympathetic reflexes initially caused greater mesenteric than renal vasoconstriction and antidiuresis and antinatriuresis only in innervated kidneys. These findings demonstrate that the intensity of hemodynamic and renal responses to stimulation of visceral receptors correlates well with the magnitude of sympathetic nerve responses.
High-energy phosphates and function in isolated, working rabbit hearts
Authors: Lewandowski E. D. , Devous MD Sr. , Nunnally R. L.
Published: December 2017

An isolated, working, rabbit heart has been developed for use with nuclear magnetic resonance (NMR) spectroscopy. This model is functionally stable over a 4-h period and displays classic hemodynamic responses to work-load changes. Control 31P spectra of this preparation (n = 5) were obtained with simultaneous recordings of left ventricular pressure (LVP), LVP differentiated with respect to time (dP/dt), heart rate (HR), and cardiac output (CO). ATP, phosphocreatine (PCr), and hemodynamics remained stable over a 90-min perfusion. Hearts were also subjected to 13.5 min of global ischemia (IS) at 37 degrees C followed by 60 min of reperfusion (RE, n = 7) or 45 min of chronic IS (n = 6). Contraction ceased within 60 s of IS. PCr loss was rapid, reaching undetectable limits by 11 min. ATP loss was gradual and bore no relationship to functional loss. ATP fell to 60 +/- 4% (means +/- SE) of pre-IS levels after 13.5 min of IS. With RE, PCr returned to control levels, whereas ATP values remained depressed for the entire 60 min. Functional activity resumed with RE, but dP/dt did not rise above 85 +/- 7% of preischemic values. No correlation between residual ATP at the end of IS and functional recovery during RE was evident.
Inosine preserves ATP during ischemia and enhances recovery during reperfusion
Authors: Devous MD Sr. , Lewandowski E. D.
Published: December 2017

The effects of exogenous inosine (IN) on high-energy phosphate metabolism and function in isolated, working rabbit hearts were monitored with 31P-nuclear magnetic resonance spectroscopy. Dynamic measurements of ATP and phosphocreatine (PCr) were made along with concomitant functional recordings during normal perfusion, global ischemia (IS), and reperfusion (RE). We found that 0.1 mM IN enhanced the rate of pressure development (dP/dt) within the left ventricle by 10 +/- 5% (n = 7). Although IN levels in treated hearts were elevated during normal perfusion, no effect was observed on ATP or PCr levels. However during IS, pretreatment with IN minimized ATP loss for the first 20 min relative to untreated controls (UNT, P less than 0.05). Both IN and UNT hearts that were ischemic for only 13.5 min regained function during a 60-min RE period. However, at the end of IS, IN hearts (n = 8) displayed 88 +/- 10% of the pre-IS ATP levels, whereas UNT hearts (n = 7) retained only 60 +/- 10%. With RE, ATP in IN hearts remained elevated over that of UNT hearts for the entire 60 min. IN treatment also increased the rate of recovery of dP/dt and maintained improved function over 60 min of RE. No correlation was found between post-IS ATP levels and dP/dt values during RE in either IN or UNT hearts. These data indicate that IN was protective against ATP loss during IS and improved functional recovery on RE.
Cholinergic vasodilation of intracerebral arterioles in rats
Authors: Dacey R. G. , Bassett J. E.
Published: December 2017

Much morphological and physiological evidence indicates that cholinergic mechanisms play a significant role in the control of cerebral blood flow. Despite in situ data suggesting that an intrinsic cholinergic mechanism produces vasodilation in the intracerebral microcirculation, there is no direct information on the effect of acetylcholine (ACh) on intracerebral arterioles. We investigated cholinergic mechanisms in isolated perfused intracerebral arterioles from pentobarbital sodium-anesthetized Sprague-Dawley rats. In arterioles with resting diameters of 46.8 +/- 6.6 microns (mean +/- SE) ACh produced no significant dilation at pH 7.30. At pH 7.60, however, a significant dose-dependent dilation to a maximum of 119.0 +/- 1.0% of control diameter was observed. Carbachol, a long-acting cholinergic agonist, similarly failed to dilate vessels at pH 7.30 but significantly dilated vessels at pH 7.60. Prostaglandin F2 alpha produced a maximum contraction to 68.3 +/- 2.7% of control diameter (n = 8). ACh at concentrations of 10(-4) and 2 X 10(-4) M induced a significant dilation of this prostaglandin-induced contraction. In vessels similarly preconstricted with serotonin, 10(-4) M ACh produced significant dilation. Atropine, having no effect on vessel diameter when administered alone, blocked cholinergic vasodilation of intracerebral arterioles at pH 7.60. Attempts at endothelial removal, although successful in eliminating endothelial cells from the preparation, significantly impaired smooth muscle contractility. ACh has no significant effect on the spontaneous cerebrovascular tone in this preparation, but in vessels preconstricted by a variety of means it produced vasodilation mediated by atropine sensitive receptors.
Development of coronary collateral circulation in left circumflex Ameroid-occluded swine myocardium
Authors: Roth D. M. , Maruoka Y. , Rogers J. , White F. C. , Longhurst J. C. , Bloor C. M.
Published: December 2017

Coronary collateral development was examined in 34 pigs after gradual occlusion of the left circumflex coronary artery (LCX) with an Ameroid constrictor. Collateral development was assessed by measurements of myocardial blood flow and regional myocardial function at rest and during exercise over a 16-wk period after placement of the constrictor. Coronary collateral development was adequate to prevent severe infarction and restore blood flow to the collateral-dependent LCX region within 3-7 wk. Infarction averaged 5.0 +/- 1.3% of the LCX region. Blood flows at rest were 1.05 +/- 0.14 and 1.13 +/- 0.15 ml.min-1.g-1 in the subendocardium of the collateral and control regions, respectively, 7 wk postoperatively. Concurrently, collateral vessel development supported normal myocardial function at rest as determined by systolic wall thickening in the LCX region. However, collateral development was limited, since blood flows during moderate and severe exercise were reduced in the LCX region compared with control and left anterior descending and right coronary regions. Blood flow ratios (collateral/control flow) during severe exercise 3 wk postoperatively were 0.23 +/- 0.03 and 0.57 +/- 0.05 in the subendocardium and subepicardium and were constant throughout the 16-wk period throughout the study. Myocardial function of the collateral region also was reduced during exercise and a 30-min recovery period. We suggest that this limited coronary collateral circulation, which develops in response to gradual coronary occlusion in swine, serves as a model for the human collateral circulation for the study of protocols to alter growth and development of coronary collateral vessels.
Skeletal muscle blood flow capacity: role of muscle pump in exercise hyperemia
Authors: Laughlin M. H.
Published: December 2017

An appreciation for the potential of skeletal muscle vascular beds for blood flow (blood flow capacity) is required if one is to understand the limits of the cardiorespiratory system in exercise. To assess this potential, an index of blood flow capacity that can be objectively measured is required. One obvious index would be to measure maximal muscle blood flow (MBF). However, a unique value for maximal MBF cannot be measured, since once maximal vasodilation is attained MBF is a function of perfusion pressure. Another approach would be to measure maximal or peak vascular conductance. However, peak vascular conductance is different among skeletal muscles composed of different fiber types and is a function of perfusion pressure during peak vasodilation within muscle composed of a given fiber type. Also, muscle contraction can increase or decrease blood flow and/or the apparent peak vascular conductance depending on the experimental preparation and the type of muscle contraction. Blood flows and calculated values of conductance appear to be greater during rhythmic contractions (with the appropriate frequency and duration) than observed in resting muscle during what is called "maximal" vasodilation. Moreover, dynamic exercise in conscious subjects produces the greatest skeletal muscle blood flows. The purpose of this review is to consider the interaction of the determinants of muscle blood flow during locomotory exercise. Emphasis is directed toward the hypothesis that the "muscle pump" is an important determinant of perfusion of active skeletal muscle. It is concluded that, during normal dynamic exercise, MBF is determined by skeletal muscle vascular conductance, the perfusion pressure gradient, and the efficacy of the muscle pump.
Quantification of calcium paradox in neonatal rat hearts
Authors: Elz J. S. , Nayler W. G.
Published: December 2017

Many indexes of damage have been used to quantify the calcium (Ca2+) paradox. We report here how different conclusions may be reached concerning the severity of the paradox when different indexes of damage are used. Hearts from 3- to 24-day-old and adult rats were isolated, depleted of Ca2+ for 5 min, and then Ca2+ repleted. Myoglobin loss, Ca2+ gain, and ultrastructural changes were monitored. Our results indicate that with increasing age each of these parameters shows a progression toward the adult state. However, this progression does not proceed at the same rate for each parameter. There was very little release of myoglobin from hearts of rats of less than 11 days old, but the amount released increased with increasing age. There appeared to be a direct relationship between the amount of myoglobin released and the proportion of extremely contracted cells with disrupted sarcolemma. However, hearts from rats of all ages gained Ca2+, suggesting that Ca2+ entry occurs via contracture-dependent and contracture-independent routes. Thus we are able to dissociate Ca2+ gain from the development of contracted cells and myoglobin release at the youngest ages. Different conclusions could therefore be reached as to the severity of the Ca2+ paradox at these youngest ages depending on which indexes of damage are documented.
The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction
Authors: Bolli R. , Patel B. S. , Zhu W. X. , O'Neill P. G. , Hartley C. J. , Charlat M. L. , Roberts R.
Published: December 2017

Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals, but the mechanism by which they produce myocellular damage remains unknown. Since iron catalyzes formation of hydroxyl radicals (HO.) as well as HO.-initiated lipid peroxidation, we explored the potential role of this metal in the pathogenesis of myocardial stunning. Open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received the iron chelator desferrioxamine intravenously (10 mg/kg over 45 min beginning 30 min before occlusion, then 1.7 mg.kg-1.h-1 throughout REP, n = 19) or normal saline (n = 17). Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. After REP, however, recovery of contractile function (expressed as percent systolic thickening) as considerably greater in desferrioxamine-treated compared with control dogs: 5 +/- 3 (mean +/- SE) vs. -3 +/- 2% (P less than 0.05) at 1 h, 6 +/- 3 vs. -2 +/- 3% (P less than 0.05) at 2 h, 5 +/- 3 vs. -6 +/- 2% (P less than 0.005) at 3 h, and 6 +/- 3 vs. -6 +/- 2% (P less than 0.002) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that iron-catalyzed reactions (possibly HO. generation) play a significant role in myocardial stunning after a brief episode of reversible regional ischemia.
Ventricular systolic interdependence: volume elastance model in isolated canine hearts
Authors: Maughan W. L. , Sunagawa K. , Sagawa K.
Published: December 2017

To analyze the interaction between the right and left ventricle, we developed a model that consists of three functional elastic compartments (left ventricular free wall, septal, and right ventricular free wall compartments). Using 10 isolated blood-perfused canine hearts, we determined the end-systolic volume elastance of each of these three compartments. The functional septum was by far stiffer for either direction [47.2 +/- 7.2 (SE) mmHg/ml when pushed from left ventricle and 44.6 +/- 6.8 when pushed from right ventricle] than ventricular free walls [6.8 +/- 0.9 mmHg/ml for left ventricle and 2.9 +/- 0.2 for right ventricle]. The model prediction that right-to-left ventricular interaction (GRL) would be about twice as large as left-to-right interaction (GLR) was tested by direct measurement of changes in isovolumic peak pressure in one ventricle while the systolic pressure of the contralateral ventricle was varied. GRL thus measured was about twice GLR (0.146 +/- 0.003 vs. 0.08 +/- 0.001). In a separate protocol the end-systolic pressure-volume relationship (ESPVR) of each ventricle was measured while the contralateral ventricle was alternatively empty and while systolic pressure was maintained at a fixed value. The cross-talk gain was derived by dividing the amount of upward shift of the ESPVR by the systolic pressure difference in the other ventricle. Again GRL measured about twice GLR (0.126 +/- 0.002 vs. 0.065 +/- 0.008). There was no statistical difference between the gains determined by each of the three methods (predicted from the compartment elastances, measured directly, or calculated from shifts in the ESPVR). We conclude that systolic cross-talk gain was twice as large from right to left as from left to right and that the three-compartment volume elastance model is a powerful concept in interpreting ventricular cross talk.
Role of contraction in the structure and growth of neonatal rat cardiocytes
Authors: Marino T. A. , Kuseryk L. , Lauva I. K.
Published: December 2017

The aim of this study was to determine the role of contraction in the regulation of neonatal rat cardiocyte growth in size. To accomplish this objective, experiments were done on four groups of cardiocytes: 1) quiescent cardiocytes attached to a substrate, 2) contracting cardiocytes attached to a substrate, 3) quiescent cardiocytes not attached to a substrate, adn 4) contracting cardiocytes not attached to a substrate. The cardiocytes were grown in both serum-free and serum-supplemented media for up to 1 wk, and cardiocyte surface area, volume, number, and fine structure were evaluated. The most important result of this study was that cardiocytes, which are attached to a substrate and stimulated to contract, grow in size. However, neither contraction alone nor attachment to a substrate by itself resulted in neonatal cardiocyte growth in size in defined serum-free medium. Another important finding was that other nonspecific growth promoters, such as those found in serum, stimulated more substantial growth in cardiocyte size in contracting cardiocytes that were attached to a substrate.
Impairment of endothelium-dependent responses of cerebral arterioles in chronic hypertension
Authors: Mayhan W. G. , Faraci F. M. , Heistad D. D.
Published: December 2017

The goal of this study was to determine whether endothelium-dependent responses are impaired in the cerebral microcirculation of stroke-prone spontaneously hypertensive rats (SHRSP). We measured diameters of cerebral arterioles using intravital microscopy in normotensive rats (WKY) and SHRSP (6-8 mo old). Cerebral vasodilator responses to superfusion with adenosine, which is an endothelium-independent agonist, were similar in WKY and SHRSP. In contrast, cerebral vasodilator responses to superfusion with endothelium-dependent agonists were profoundly impaired in SHRSP. Acetylcholine (10(-4) M) increased pial arteriolar diameter 23 +/- 2% (means +/- SE) in WKY and did not change arteriolar diameter in SHRSP (-2 +/- 3%, P less than 0.05 vs. WKY). Serotonin (10(-5) M) increased pial arteriolar diameter 23 +/- 1% in WKY and, in contrast, reduced diameter 11 +/- 1% in SHRSP (P less than 0.05 vs. WKY). Nitroglycerin and acetylcholine produce vasodilatation by activation of guanosine 3',5'-cyclic monophosphate (cGMP). Nitroglycerin was used to determine whether impaired responses of cerebral arterioles in SHRSP were related to altered cGMP activity. We found similar dilatation of cerebral arterioles in WKY and SHRSP in response to nitroglycerin. Thus impaired endothelium-dependent dilatation in SHRSP is not related to alteration of cGMP activity. We speculate that impairment of cerebral vasodilator responses to endothelium-dependent agonists, including vasoactive substances released by platelets, may predispose SHRSP to cerebral ischemia.
Atrial natriuretic peptide transcription, storage, and release in rats with myocardial infarction
Authors: Mendez R. E. , Pfeffer J. M. , Ortola F. V. , Bloch K. D. , Anderson S. , Seidman J. G. , Brenner B. M.
Published: December 2017

To study the role of atrial natriuretic peptide (ANP) in chronic heart failure, ANP synthesis, storage, and release were examined by measuring atrial ANP messenger ribonucleic acid (mRNA) levels and atrial and plasma ANP concentrations in rats with myocardial infarction produced by coronary artery ligation. Three groups were defined as the following: 1) controls, sham-operated, or operated, but noninfarcted; 2) moderate infarcts, involving 5-30% of the left ventricular circumference; and 3) large infarcts (greater than or equal to 30%). In addition, to determine a possible modulation by dietary Na intake on ANP levels in heart failure, plasma immunoreactive ANP (iANP) levels were measured in rats with and without infarcts given low, regular, or high Na intake for 2 wk, by which time all groups were in neutral balance. Plasma iANP levels varied directly with increasing infarct and atrial sizes, irrespective of Na intake. In contrast, atrial ANP concentration varied inversely with increasing infarct size. The ANP mRNA content index, a measure of total atrial ANP mRNA, was significantly increased in rats with large infarcts compared with control rats. These results indicate that in rats with myocardial infarction, the severity of left ventricular dysfunction, as inferred from infarct size, but not chronic Na intake, is the primary determinant of the extent of activation of the ANP system. Elevated circulating ANP levels are maintained through enhanced atrial synthesis and release. ANP may thus play an important role in the hemodynamic and renal adaptations to chronic heart failure.
Prostacyclin reduces "preload" in conscious dogs via a vagal reflex mechanism
Authors: Nganele D. M. , Hintze T. H.
Published: December 2017

The purpose of this study was to determine the effects of prostacyclin on left ventricular (LV) preload in conscious dogs. LV end-diastolic diameter (LV EDD) was used as an index of preload. Because prostacyclin reduces arterial pressure, data were sampled when mean arterial pressure, heart rate, and first derivative of LV pressure (dP/dt) had returned to control levels. There was no dose-response relationship in the preload reduction to prostacyclin, the threshold dose being 0.1 microgram/kg. Intravenous prostacyclin (2.0 micrograms/kg) reduced LV EDD 2.9 +/- 0.5% from 36 +/- 2.2 mm, (P less than 0.01). With heart rate held constant (146 +/- 2.5 beats/min) by electrical pacing, prostacyclin still reduced LV EDD by 4.0 +/- 1.0% from 32 +/- 2.5 mm (P less than 0.05). Intravenous administration of arachidonic acid (500 micrograms/kg) gave similar results. The magnitude of the preload response to prostacyclin was similar to that of nitroglycerin (25 micrograms/kg). Prazosin (1 mg/kg) or bilateral cervical vagal section completely abolished the preload response to prostacyclin but not to nitroglycerin. We, therefore, propose a mechanism where prostacyclin activates cardiopulmonary receptors with vagal afferents that results in a withdrawal of peripheral sympathetic tone to capacitance vessels to reduce preload, in contrast to nitroglycerin, whose mechanism of action is most probably a direct effect on capacitance vessels.
Modulation of vascular smooth muscle sensitivity by preload and eicosanoid synthesis inhibition
Authors: Herlihy J. T. , Johns A. , Harper M. J.
Published: December 2017

An increase in preload from 0.75 to 10 g caused an increase in the sensitivity of rabbit aortic strips to phenylephrine, serotonin, and KCl. Several eicosanoid synthesis inhibitors were utilized to determine whether production of endogenous eicosanoids contributed to the change in muscle sensitivity. Quinacrine (10 microM), indomethacin (10 and 50 micrograms/ml), meclofenamate (50 and 100 micrograms/ml), 5,8,11,14-eicosatetraynoic acid (ETA, 50 and 100 micrograms/ml), and nordihydroguaiaretic acid (NDGA, 10 microM) all shifted the concentration-response curves of various agonists to the right, indicating a decrease in the sensitivity of the muscle to these agents. Thromboxane synthesis inhibition by 1 microM (E)-3-[4-(1-imidazolylmethyl]phenyl-2-propenoate (OKY 046) exerted no effect on sensitivity. Indomethacin at both concentrations caused a parallel shift in the high and low preloaded strips but was unable to alter the influence of preload on sensitivity. A similar effect was observed with the lower concentrations of meclofenamate and ETA. NDGA and higher concentrations of meclofenamate and ETA not only shifted the sensitivity in both high and low preloaded strips but also eliminated the preload effect. These results indicate that cyclooxygenase and lipoxygenase metabolites both alter aortic smooth muscle sensitivity to contractile agents and suggest that lipoxygenase metabolites may play a role in the change in sensitivity seen with preload.
Modification of force-interval relations during early adaptation to pressure overload in dogs
Authors: Crozatier B. , Hittinger L. , Chavance M.
Published: December 2017

Ventricular function was analyzed in the end-systolic and end-ejection pressure-volume diagrams in seven conscious dogs during acute aortic stenosis (AS) and sustained stenosis (SS) 24 h later. Dogs were previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular major and minor axes and parietal wall thickness. The end-ejection pressure-calculated volume points were significantly shifted to the left during SS as compared with those obtained during AS both during a regular atrial pacing (150 beats/min) and during spontaneous heart rate. Postpacing beats were not different during AS and SS. During AS, end-systolic volume was larger after short intervals (SI) between beats (22.5 +/- 1.6 ml) than after long intervals (LI; 20.8 +/- 1.7 ml) for a smaller end-systolic pressure (P less than 0.001). This difference was minimal during SS. When SS was compared with AS, the end-systolic and end-ejection pressure-volume points were significantly shifted to the left after SI but not after LI. This suggests an acceleration of the restitution process during SS that modifies ventricular force-frequency relations and increases ventricular function as compared with AS, particularly for high heart rates.
Renal vascular reactivity to U 46619 and adrenergic agonists in Goldblatt hypertension
Authors: Zimmerman B. G.
Published: December 2017

Vascular reactivity of the contralateral kidney of conscious Goldblatt hypertensive dogs was studied by eliciting renal blood flow (RBF) responses to intra-arterial infusions of vasoconstrictor and vasodilator agonists in control sessions and at weekly intervals postclipping. Systemic arterial blood pressure (BP) and RBF were monitored during each recording session via an implanted catheter and electromagnetic blood flow probe, respectively. BP was maximally increased within 1 wk and remained elevated for the duration of the study. The relationship between the negative percent change in RBF (-% delta RBF) and the renal arterial plasma concentration of adrenergic agonists, angiotensin II and thromboxane mimetic (U 46619), infused intra-arterially was subjected to regression analysis, and 25 and 50% effective doses (ED25 and ED50, respectively) were calculated. Vascular sensitivity to phenylephrine and norepinephrine increased within a month or more of hypertension. Vascular reactivity to angiotensin II was unchanged. In contrast to the delayed increase in renal vascular reactivity to adrenergic agonists, enhancement of the RBF responses to U 46619 was seen within 1-2 wk. In addition, beta-adrenoceptor-mediated vasodilation appeared suppressed during hypertension. Alteration in the response of the contralateral kidney to both vasoconstrictor and beta-adrenoceptor-mediated vasodilator stimuli may contribute to renal hemodynamic changes in Goldblatt hypertension.
Fluid exchange in skeletal muscle with viscoelastic blood vessels
Authors: Lee J. , Salathe E. P. , Schmid-Schonbein G. W.
Published: December 2017

A mathematical model of capillary-tissue fluid exchange in a viscoelastic blood vessel is presented, and the Landis occlusion experiment is simulated. The model assumes that the fluid exchange is governed by Starling's law and that the protein and red blood cells are conserved in the capillary. Before occlusion, in the steady flow state, the pressure in the capillary decreases from the arterial to venous end due to viscous dissipation. After occlusion a constant pressure is established along the capillary. We assume the capillary to be distensible with viscoelastic wall properties. Immediately following occlusion an instantaneous distension of the capillary occurs. The vessel continues to expand viscoelastically while fluid is filtered for a period of several minutes, until it reaches an equilibrium state. A full numerical solution of the governing equations has been obtained. We use this model to compute the distance variation between two labeled erythrocytes as obtained in the Landis occlusion experiment and compare the results with experimental data obtained recently for the spinotrapezius muscle in our laboratory. The new model can fit the experimental data better than previous models that neglect the distensibility of the capillaries.
Angiotensin II binding sites in the conduction system of rat hearts
Authors: Saito K. , Gutkind J. S. , Saavedra J. M.
Published: December 2017

Angiotensin II binding sites were localized and quantified in the conduction system of the rat heart by autoradiography in combination with computerized microdensitometry. Tissue sections (16-microns thick), containing cardiac vagus ganglia, sinus node, and atrioventricular node, were incubated with 125I-Sar1-angiotensin II to generate autoradiograms that were compared with other autoradiograms from 125I-labeled standards. Angiotensin II binding sites were highly localized in both the sinoatrial and atrioventricular nodes and in the cardiac vagus ganglia. In contrast, binding to the angiotensin converting enzyme, determined by incubation of adjacent tissue sections with the specific enzyme inhibitor 125I-351A, was very low in these areas but high in the cardiac endothelium. Our results suggest that angiotensin II may have direct chronotropic effects through stimulation of specific receptors in the conduction system of the heart and in intrinsic parasympathetic ganglia.
Effect of hemodilution on oxygen transport in arteriolar networks of hamster striated muscle
Authors: Kuo L. , Pittman R. N.
Published: December 2017

Page H339: L. Kuo and R. N. Pittman. “Effect of hemodilution on oxygen transport in arteriolar networks of hamster striated muscle.” Reference 22 should appear as follows.

22. Pittman, R. N., and B. R. Duling. Measurement of percent oxyhemoglobin in the microvasculature. J. Appl. Physiol. 38: 321–327, 1975.
Time course and determinants of recovery of function after reversible ischemia in conscious dogs
Authors: Bolli R. , Zhu W. X. , Thornby J. I. , O'Neill P. G. , Roberts R.
Published: December 2017

The postischemic recovery of contractile function [measured as systolic wall thickening (WT)] was analyzed in 21 conscious dogs undergoing a 15-min coronary occlusion followed by 7 days of reperfusion (REP). Average WT was still depressed 24 h after REP (85% of base line, P less than 0.001) and returned to base line by 48 h. Analysis of individual dogs, however, revealed marked variability, whereby some recovered completely by 1 h of REP and others required up to 48 h. WT recovered completely within 30 min in dogs with collateral blood flow (CBF) greater than 50% of nonischemic zone flow (NZF) but was still impaired at 24 h (P less than 0.05) in those with CBF less than 25% of NZF. There was a close, curvilinear relation between WT during the first 4 h of REP and transmural CBF, which was described best by an exponential equation WT (as percent of base line) = P0-P1e-P2.CBF(as % of NZF) (r2 = 0.92 at 1 h, 0.76 at 2 h, 0.71 at 3 h, and 0.72 at 4 h), where P0, P1, and P2 are regression coefficients. Importantly, the slope of the regression line was very steep at low CBF, implying that even small differences in CBF produce large differences in postischemic function. Heart rate, systolic pressure, and rate-pressure product during ischemia were also related to WT after REP, but when the effect of CBF was taken into account, the influence of these variables became insignificant. The size of the occluded vascular bed did not correlate with postischemic WT. The presence of hypokinesis or akinesis during ischemia was associated with rapid recovery after REP, but there was no relation between ischemic and postischemic dysfunction when dyskinesis was present during occlusion. Thus, on the average, regional function remains depressed for 24 h after a 15-min ischemic episode, but there is considerable individual variability. This variable rate of recovery is determined primarily by the severity of blood flow reduction during ischemia. Systemic hemodynamics may modulate recovery of function indirectly via their effects on ischemic blood flow.
Cardiac gap junction channel activity in embryonic chick ventricle cells
Authors: Veenstra R. D. , DeHaan R. L.
Published: December 2017

We have recorded single-gap junction-channel currents from pairs of 7-day chick embryo ventricle cells, using the double whole cell patch-clamp technique. Junctional conductance (Gj) was variable from one preparation to the next, ranging from 0.15 to 35.0 nS. Single-channel conductance (gamma j) of the main junctional channel was 166 +/- 51 pS and was independent of Gj; a second conductance level of 60–80 pS was also seen in favorable records. The transition time from the closed to the open state was 285 +/- 153 microseconds, with some slow transitions lasting 1–5 ms. Channels opened and closed stochastically; Gj could be defined by the product of the number of active channels in the junction (N), the mean open-state probability (Po) of the channels, and gamma j. Channel activity was unaffected by cell membrane potential or by transjunctional potential. Po and Gj were reversibly reduced to low levels by 1-octanol or by elevated [Cai], whereas gamma j was unchanged by these agents. The 60–80 pS conductance mechanism was octanol- and Ca-resistant, but it is not clear whether this represents a subconductance level of the main channel or a separate class of smaller channels.
Mechanism of diminished contractile response to catecholamines during acidosis
Authors: Marsh J. D. , Margolis T. I. , Kim D.
Published: December 2017

To examine mechanisms of diminished contractile response to catecholamines during acidosis, we studied contractile properties, beta-adrenergic receptor properties, and intracellular pH of intact, cultured myocardial cells from chick embryo ventricle at pH 7.4 and 6.8. Contractile response was measured with an optical-video system. On changing the superfusing buffer from pH 7.4 to 6.8 there was a decline in contractile amplitude to 80% of control by 20 min. Fluorimetrically determined intracellular pH declined over a similar time course from 7.11 +/- 0.05 to 6.96 +/- 0.07 (P less than 0.05). After 45 min at pH 6.8 the contractile response to 1 microM isoproterenol was less than half of the response at pH 7.4. Antagonist and agonist ligand-binding properties of the beta-adrenergic receptor were determined in the intact cells under conditions identical to those for the contractility studies. With the use of the hydrophilic antagonist [3H]CGP-12177 that selectively labels cell-surface receptors, agonist competition studies demonstrated that acidosis had no significant effect on antagonist or agonist affinity but decreased beta-receptor number from 21 +/- 3 to 11 +/- 3 fmol/mg protein (P less than 0.02). It is probable that a decline in the number of beta-receptors on the cell surface contributes to contractile hyporesponsiveness to catecholamines during acidosis.
Spontaneous vasomotion in pressurized cerebral arteries from genetically hypertensive rats
Authors: Osol G. , Halpern W.
Published: December 2017

Resistance-sized branches of posterior cerebral arteries from Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), spontaneously hypertensive stroke-prone (SHRSP), and antihypertensive-treated SHRSP (SHRSP-TRT) rats were studied in vitro. After the rats were killed, arterial segments were excised, mounted on microcannulas, and pressurized. After equilibration, intravascular pressure was increased in a stepwise fashion from 30 to 150-200 mmHg. All vessels developed a myogenic tone, which resulted in diameter reductions of 31-37% at 100 mmHg when compared with fully relaxed diameters [approximately 200 micron in 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid]. Differences in the extent of tone were not significant between animal groups (P greater than 0.05). Rhythmic vasomotion was present in 94% SHRSP and 100% SHRSP-TRT, 83% SHR, and only 6% of the WKY arteries. At higher pressures, the amplitude of the diameter oscillations decreased and frequency increased. Vasomotion was unaltered by tetrodotoxin or indomethacin, but could be abolished by cooling to 34 degrees C, ouabain (a depolarizing solution containing 125 mM K+), potassium-free physiological saline solution, or by calcium entry blockade with diltiazem or MnCl2. In normally quiescent WKY arteries, vasomotion, which was qualitatively similar to that observed in the hypertensive strains, could be induced by the addition of 5 mM tetraethylammonium chloride. Thus intrinsic oscillations in membrane calcium and potassium conductance may underlie the rhythmic contractile activity of rat cerebral arteries. This property appears to have a major genetic component, the expression of which is relatively independent of blood pressure history and is not related to the myogenic properties of the preparation.
Computer analysis of cardiovascular changes during sleep-wake cycle in Sprague-Dawley rats
Authors: Lacombe J. , Nosjean A. , Meunier J. M. , Laguzzi R.
Published: December 2017

Blood pressure (BP) and heart rate (HR) were recorded in seven Sprague-Dawley rats during a total of 491 normal sleep-wake cycles with the use of a computer-assisted method developed for this study. Significant changes of BP, HR, and BP variability (BPV) were found between the three states within the cycle, i.e., wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS). The highest BP, BPV, and HR values were found during W. Then all cardiovascular (CV) variables fell during SWS, whereas BP and BPV rose again during PS. The fall of BPV observed during SWS was the most important CV change observed within the cycle. These state-dependent CV changes suggest that, in the rat, circulation during the sleep-wake cycle is controlled by the same central factors that operate in cats. In addition, significant BP and HR modifications between different cycles have been found. On the other hand, BP and HR differences between animals were also observed. The latter differences were found to be stable across the states, but no significant relation was found between BP and HR within any state. Thus the present data also suggest that BP and HR measurements are influenced not only by state-dependent factors but also by at least three different factors that are each independent of the state: one leads to BP and HR values that are influenced by the cycle the animal is in and the other two influence, respectively, the ranking of the individual's BP and HR levels within the population.
Bioassay by cross-perfusion for circulating inotropic factor in hypertension
Authors: Overbeck H. W.
Published: December 2017

To study inotropic effects of blood from one-kidney, one-clip (1K,1C) rats with early (less than 7 days) or chronic (greater than 4 wk) benign hypertension, we assessed arteriolar resistance and norepinephrine (NE) responses in vascularly isolated, innervated assay hindlimb vascular beds of alpha-chloralose-anesthetized, normal male recipient rats. Hindlimbs were cross-perfused (2 ml/min) with blood from anesthetized donor rats with limb outflow returned to the donor rat. Perfusion pressure was monitored. Complete NE (injected intra-arterially) dose-response curves in limbs perfused with donor blood from nine early 1K,1C rats, compared with nine appropriate normotensive control donor rats, indicated unchanged thresholds, 50% effective doses, and maximal responses. Curves in limbs perfused with blood from 10 chronic 1K,1C, compared with 10 appropriate controls, suggested small (P less than 0.02) leftward shifts. Decreases (P less than 0.01) in maximal responses were also observed. Limb resting resistance and minimal resistance (sodium nitroprusside) did not rise, even after 4-5 h of cross-perfusion. These results provide no evidence in early 1K,1C and little evidence in chronic 1K,1C that humoral factors, including ouabainlike inhibitors, evoke physiologically significant inotropic effects in arterioles in vivo.
T3 treatment does not prevent myocardial dysfunction in chronically diabetic rats
Authors: Barbee R. W. , Shepherd R. E. , Burns A. H.
Published: December 2017

The isolated working heart preparation was used to investigate the effect of continuous triiodothyronine (T3) administration on cardiac function and metabolism of rats rendered diabetic for a period of 4 wk with streptozocin (STZ). T3 controlled-release pellets were implanted 1 wk after STZ (70 mg/kg) injection. Rats injected with citrate buffer without STZ received T3 pellets 1 and/or 2 wk later. A comparable number of rats received placebo pellets. Untreated diabetic rats exhibited a decrease in spontaneous heart rate and myocardial cytochrome c concentrations concurrent with depressed plasma T3 values compared with untreated controls. T3 treatment did not improve in vitro cardiac performance (assessed as cardiac output times peak systolic pressure per gram dry heart weight) in hearts from diabetic rats perfused with glucose alone. Addition of octanoate reversed this depression and improved cardiac function to a greater extent in treated than in untreated diabetic animals. However, these differences between treated and untreated diabetic animals disappeared when heart rate was controlled by cardiac pacing. Furthermore, T3 treatment of controls and diabetics did not alter the oxidation of octanoate or the cardiac responsiveness to isoproterenol. These results suggest that experimental diabetic cardiomyopathy is partly attributable to a substrate deficiency and is not due entirely to hypothyroidism.
O2 consumption of dog heart under decreased coronary perfusion and propranolol
Authors: Suga H. , Goto Y. , Yasumura Y. , Nozawa T. , Futaki S. , Tanaka N. , Uenishi M.
Published: December 2017

We compared the effects of decreased coronary perfusion pressure (CP) and propranolol on the relation between left ventricular O2 consumption (VO2) and systolic pressure-volume area (PVA). PVA represents total mechanical energy generated by contraction and is the area under the end-systolic pressure-volume (PV) line and systolic PV trajectory. In excised cross-circulated dog hearts, a decrease in CP from 82 (mean) to 51 mmHg decreased ventricular contractility index Emax (slope of end-systolic PV relation) by 17% (P less than 0.05) and slightly (P less than 0.05 in 3 of 11 hearts) lowered the VO2-PVA relation in a parallel fashion. A further decrease in CP to 32 mmHg decreased Emax by 56% (P less than 0.05) and considerably (P less than 0.05) lowered the VO2-PVA relation by decreasing both the VO2-axis intercept by 26% (P less than 0.05) and the slope by 24% (P less than 0.05) from control. Propranolol decreased Emax by 48% (P less than 0.05) and the VO2-axis intercept by 25% (P less than 0.05) without changing the slope (P greater than 0.05). We attributed the different response of the VO2-PVA relation to the difference of the coronary O2 supply-demand balance between decreased CP and propranolol.
Effect of hemodilution on oxygen transport in arteriolar networks of hamster striated muscle
Authors: Kuo L. , Pittman R. N.
Published: December 2017

Experiments were performed on the hamster cheek pouch retractor muscle to investigate the influence of isovolemic hemodilution on microcirculatory hemodynamics and the rate of oxygen transport to striated muscle. In 23 hamsters, measurements of red blood cell velocity, hematocrit, vessel diameter, segment length (L), hemoglobin oxygen saturation (SO2), and longitudinal SO2 gradient (delta SO2/L) were made in four branching orders of arterioles before and after isovolemic exchange with plasma. Hemodilution decreased systemic hematocrit from 52 to 33%. In first- through fourth-order arterioles, this degree of hemodilution resulted in an average decrease in microcirculatory hematocrit from 42 to 28% and average increases in red blood cell velocity, computed blood flow, and systemic arterial PO2 of 50, 30, and 10%, respectively. In addition, delta SO2/L was significantly smaller in second-, third-, and fourth order arterioles compared with control values. It was estimated that approximately 84% of the oxygen that diffused across the arteriolar network was transferred by diffusion to nearby venules and capillaries; the remaining oxygen was consumed by the surrounding tissue. Following hemodilution, the magnitude of diffusional transfer declined to 73%. Oxygen flow remained at its control level in the first-order arterioles and progressively increased above control with increasing branching order. The increased oxygen delivery to the capillary network after limited hemodilution can be attributed to a compensatory increase in blood flow, an increase in systemic arterial blood oxygenation, and a decrease in precapillary oxygen loss.