bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic lability of the arterial blood pressure produced by electrolytic lesions of the nucleus tractus solitarii in the rat.
Authors: Buchholz R A , Nathan M A
Published: June 2012

The purpose of this study was to assess the chronic effects of lesions of the nucleus tractus solitarii on the cardiovascular activity of rats. Arterial pressure and heart rate were recorded in conscious, unrestrained rats 7-216 days following placement of electrolytic lesions in the nucleus tractus solitarii. To assess the impact of environmental stimuli on the mean level and lability of the mean arterial pressure, cardiovascular activity was recorded under conditions of controlled and uncontrolled environmental stimulation. Nucleus tractus solitarii lesions abolished the reflex bradycardia to a phenylephrine-induced elevation in arterial pressure. A marked increase in the lability of the mean arterial pressure was produced with nucleus tractus solitarii lesions. The standard deviation of the mean arterial pressure, an index of lability, was 380% greater in rats with lesions than in control rats. The average mean arterial pressure, heart rate and heart rate variability were not significantly different between the lesion and control groups, regardless of the environmental conditions under which the measurements were made. Nucleus tractus solitarii lesions also greatly exaggerated the arterial pressure response to naturally occurring behaviors, such as eating and drinking. Vagal and beta-adrenergic blockade with methyl atropine and propranolol did not alter the average level or lability of the mean arterial pressure, although heart rate responses were similar in both groups. alpha-Receptor blockade with prazosin significantly lowered the mean arterial pressure in both lesion and control rats, but the decrease in mean arterial pressure was significantly greater in rats with nucleus tractus solitarii lesions (42 +/- 6 mm Hg, 38.5%) than in control rats (27 +/- 4 mm Hg, 23.2%). Prazosin also reduced the lability of the mean arterial pressure to control levels in rats with lesions. Thus, the chronic effects of nucleus tractus solitarii lesions in rats are to abolish the cardiomotor component of the baroreflexes and to produce extreme lability of the arterial pressure without altering the average level of the mean arterial pressure. Exaggerated blood pressure responses are seen in association with various behaviors. These effects are mediated primarily by changes in sympathetic discharge to the vasculature and are independent of the ambient level of environmental stimuli.
Inhibitory influences from arterial baroreceptors on vasopressin release elicited by fastigial stimulation in rats.
Authors: Del Bo A , Sved A F , Reis D J
Published: June 2012

Electrical stimulation of the fastigial nucleus in anesthetized, paralyzed, and artificially ventilated rats for 10 seconds (50 Hz) induced a stimulus-locked elevation of arterial pressure (the fastigial pressor response) and increased plasma vasopressin. Cervical spinal cord transection abolished the stimulus-locked fastigial pressor response and augmented the vasopressin response to a 10-fold increase (19 +/- 1 to 188 +/- 58 pg/ml, P less than 0.05; n = 8). Grading the pressor elevations occurring during the fastigial nucleus stimulus changed the amounts of vasopressin released in the same animal: acute adrenalectomy and chemosympathectomy by guanethidine reduced the magnitude of the fastigial pressor response and facilitated the vasopressin release to fastigial nucleus stimulation (intact: 52 +/- 11 pg/ml; after adrenalectomy and chemosympathectomy, 254 +/- 73 pg/ml, P less than 0.05, n = 6). Subsequent intravenous administration of a bolus of phenylephrine to increase mean arterial pressure during fastigial nucleus stimulus, as in intact situation, reduced the vasopressin release (47 +/- 9 pg/ml). After sinoaortic denervation plus vagotomy, the fastigial pressor response was preserved; however, vasopressin still increased 11-fold (from 11 +/- 1 to 126 +/- 23 pg/ml, P less than 0.01, n = 8). Vagotomy alone did not affect the vasopressin resting level nor the 4-fold increase in response to fastigial nucleus stimulation. Therefore, stimulus-locked elevations of arterial pressure oppose, by reflex mechanisms mediated through baroreceptors, but do not prevent the release of vasopressin elicited by stimulation of the fastigial nucleus.
Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids.
Authors: Chien K R , Han A , Sen A , Buja L M , Willerson J T
Published: June 2012

Studies in ischemic canine left ventricle have shown that the depletion of membrane phospholipids is a critical event in the development of a sarcolemmal calcium permeability defect and associated irreversible myocyte injury. The mechanism of phospholipid loss is unclear, but may be due to the activation of endogenous phospholipases. Since arachidonic acid is a fatty acid found almost entirely in phospholipid, increases in arachidonate provide evidence for increased phospholipase activity. The present study was designed to examine the temporal relationship of the accumulation of free arachidonate with the onset of phospholipid depletion during fixed ligation of the left anterior descending coronary artery in canine myocardium. The following results were demonstrated in ischemic canine myocardium: (1) the accumulation of unesterified arachidonate is minimal during 10-30 minutes of ischemia, but is significantly increased after prolonging the duration of ischemia to 1-3 hours; (2) significant increases in arachidonate precede the development of a significant decrease in total phospholipid content; (3) the decrease in the arachidonate content of phosphatidylcholine is accompanied by similar decreases in all of the fatty acyl moieties; (4) the arachidonate content of lysophosphatidylcholine and diacylglycerol are unchanged during myocardial ischemia; (5) there is evidence of a deacylation-reacylation cycle in phosphatidylcholine prior to the accumulation of free arachidonate; (6) the fatty acyl specificity of the lysophosphatidylcholine acyltransferase corresponds to the pattern of fatty acyl remodeling of phosphatidylcholine during early myocardial ischemia. These data suggest that the accumulation of arachidonate may be a more sensitive measure of phospholipid degradation than the decrease in total phospholipid content in ischemic canine myocardium. It is postulated that the defective reacylation of arachidonate into phosphatidylcholine may contribute to the net loss of membrane phospholipid during myocardial ischemia.
Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat.
Authors: Badr K F , Baylis C , Pfeffer J M , Pfeffer M A , Soberman R J , Lewis R A , Austen K F , Corey E J , Brenner B M
Published: June 2012

We studied the systemic and renal hemodynamic effects of leukotriene C4 (2 micrograms/kg per min for 5 minutes, iv) in the rat. During the period of its infusion, leukotriene C4 produced a significant elevation of mean arterial pressure and reductions in cardiac output and renal blood flow, as measured by electromagnetic flow probes. These effects were abolished by FPL55712 , a putative antagonist of sulfidopeptide leukotrienes, but not by saralasin or indomethacin. Leukotriene C4 also resulted in an average loss of 20% in plasma volume which, during the postinfusion period, perpetuated the low cardiac output state and thus provoked the release of angiotensin II. This vasoactive peptide sustained the elevation in systemic vascular resistance and the reduction in renal blood flow over a 70-minute postinfusion observation period. Consequently, glomerular filtration rate fell by approximately 50%. These angiotensin II-mediated effects were abolished by saralasin. Indomethacin prevented the leukotriene C4-induced loss of plasma volume and, thus, allowed for the significant recovery of cardiac output and renal blood flow during the post-infusion period, thereby preserving glomerular filtration rate. We conclude that leukotriene C4 exerts direct systemic and renal vasoconstrictor, as well as cardiodepressant effects, during the period of its infusion. By virtue of its vasopermeability enhancing effect, leukotriene C4 also results in an immediate loss of plasma volume, an effect which requires the presence of secondarily generated cyclooxygenase products and which perpetuates the hemodynamic abnormalities observed beyond the period of leukotriene C4 infusion.
Release of histamine by sympathetic nerve stimulation in the guinea pig heart and modulation of adrenergic responses. A physiological role for cardiac histamine?
Authors: Gross S S , Guo Z G , Levi R , Bailey W H , Chenouda A A
Published: June 2012

Histamine has been reported to attenuate adrenergic responses in cardiovascular tissues. In guinea pig atria preloaded with [3H]norepinephrine, histamine diminishes the field stimulation-induced efflux of radioactivity; this effect has been attributed to an inhibition of norepinephrine release from nerve endings. To assess the possible physiological relevance of these findings, we have reinvestigated the effects of histamine on cardiac sympathetic responses and on the release of endogenous norepinephrine in the guinea pig heart isolated with its intact sympathetic innervation. Heart rate, left ventricular contractile force, and perfusion pressure all increased with increasing frequencies of sympathetic nerve stimulation (2-8 Hz). Histamine (3 X 10(-8) to 3 X 10(-7) M) caused dose-dependent attenuation of the responses to sympathetic stimulation. The ability of histamine to modulate nerve stimulation-induced norepinephrine overflow into the coronary effluent was dependent on whether the heart had been preloaded with norepinephrine. Whereas histamine did not cause a significant reduction in nerve stimulation-induced norepinephrine overflow in hearts from untreated animals, histamine significantly reduced stimulation-induced norepinephrine overflow in hearts from guinea pigs that had been pretreated with norepinephrine before sacrifice. Histamine also attenuated the increases in left ventricular contractile force, perfusion pressure, and heart rate, which result from the intracardiac administration of norepinephrine (0.16-microgram bolus injection). In this respect, histamine was as effective as it was in inhibiting the responses elicited by nerve stimulation. Thus, in normal animals, the negative modulatory effect of histamine on adrenergic responses can be attributed largely, if not totally, to a postjunctional mechanism. In contrast, a prejunctional action of histamine may contribute significantly to the negative modulation observed in norepinephrine-preloaded hearts. Since we have observed a large increase in the amount of endogenous histamine present in the coronary effluent after sympathetic stimulation (930 pg during the 30 seconds poststimulation vs. 240 pg during 30 seconds prestimulation), as well as a prolongation of nerve stimulation-induced cardiac responses in the presence of the H2 receptor antagonist tiotidine, we postulate that histamine plays a physiological role as a modulator of sympathetic responses in the heart.
The effect of warming on adrenergic neurotransmission in canine cutaneous vein.
Authors: Cooke J P , Shepherd J T , Vanhoutte P M
Published: June 2012

The effect of warming on adrenergic neurotransmission was examined in canine cutaneous veins. Isometric tension was recorded from rings of saphenous veins of the dog in organ chambers filled with physiological salt solution. During contractions caused by potassium or prostaglandin F2 alpha, warming from 37 to 41 degrees C caused an augmentation. During contractions caused by stimulation of the adrenergic nerves, and by exogenous norepinephrine, warming caused a relaxation. The relaxation with warming was not altered by the beta-adrenergic antagonist, propranolol, or by inhibitors of extraneuronal and neuronal uptake of norepinephrine. During contractions evoked by the alpha 2-adrenergic agonists, alpha-methyl norepinephrine and B-HT 920, warming caused a relaxation, whereas during contractions due to the alpha 1-adrenergic agonists, cirazoline , methoxamine, ST 587, and phenylephrine, it caused an augmentation. The relaxation caused by warming during norepinephrine-induced contractions was prevented by the preferential alpha 2-antagonists yohimbine and rauwolscine, but not by the preferential alpha 1-antagonist, prazosin. In strips of saphenous vein incubated with [3H] norepinephrine , warming did not affect the release of labeled transmitter evoked by nerve stimulation. These experiments indicate that warming directly enhances contractility of vascular smooth muscle, while depressing the responsiveness of cutaneous vessels to sympathetic nerve activation by a selective inhibitory effect on postjunctional alpha 2-adrenoceptors. Relaxation with warming is greater during nerve stimulation than during administration of exogenous norepinephrine, which may be due to a predominance of postjunctional alpha 2-adrenoceptors in the neuromuscular junction.
Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins.
Authors: Pomerantz K B , Tall A R , Feinmark S J , Cannon P J
Published: June 2012

We studied the effects of plasma high density and low density lipoproteins upon the synthesis of prostacyclin and prostaglandin E2 by vascular smooth muscle cells. Prostaglandin synthesis was measured in 24-hour cultures by radioimmunoassay of the stable metabolites of prostacyclin, 6-keto-prostaglandin F1 alpha and of prostaglandin E2. High density lipoproteins induced dose-dependent increases in the release of 6-keto-prostaglandin F1 alpha and of prostaglandin E2 from smooth muscle cells to values 14- and 50-fold above control. Incubations with low density lipoproteins at comparable cholesterol concentrations also induced dose-dependent release of 6-keto-prostaglandin F1 alpha and prostaglandin E2, but to a lesser extent. Rat high density lipoprotein, which contained 2.5 times more cholesteryl arachidonate than human high density lipoproteins, stimulated 6-keto-prostaglandin F1 alpha and prostaglandin E2 release 2- to 3-fold more than human high density lipoproteins, whereas the delipidated apoproteins of high density lipoproteins had no significant effect on prostaglandin synthesis. Recombinant high density lipoproteins containing cholesteryl-[1- 14C]arachidonate stimulated release of [14C]-6-keto-prostaglandin F1 alpha and [14C]prostaglandin E2 by smooth muscle cells. The ionophore, A 23187, released labeled 6-keto-prostaglandin F1 alpha and prostaglandin E2 from cells preincubated with recombinant high density lipoprotein containing cholesteryl-[1- 14C]arachidonate. Unlabeled high density lipoproteins, in contrast, did not cause release of radioactive prostaglandins from cells preincubated with [1- 14C]arachidonate. Phospholipase activators were synergistic (bradykinin) or additive (angiotensin II) with high density lipoprotein in stimulation of prostaglandin synthesis. The data indicate that both high and low density lipoproteins stimulate the synthesis of prostacyclin and prostaglandin E2 by vascular smooth muscle cells. The results suggest that the lipoproteins provide arachidonate to a phospholipase-sensitive pool accessible to cyclooxygenase.
An atrial peptide is a potent renal vasodilator substance.
Authors: Oshima T , Currie M G , Geller D M , Needleman P
Published: June 2012

Renal intra-arterial administration of rat atrial extracts elicits a concentration dependent renal vasodilation (independent of prostaglandin or dopamine release) in anesthetized rats. The atrial extracts do not alter skeletal musculature (hindlimb) vascular resistance or systemic arterial blood pressure. The high molecular weight peptide fraction of atrial extracts obtained by gel filtration, reduces renal resistance intra-arterially only after proteolytic activation (in vitro) or following intravenous (i.e., systemic in vivo activation) administration. The low molecular weight peptide fraction of the atrial extract which is active intra-arterially as a renal vasodilator has been further purified to yield two major peptides. The 21 amino acid peptide, designated atriopeptin I, was previously demonstrated to be natriuretic and to relax intestinal but not vascular smooth muscle strips. This peptide exerted little or no intra-arterial effect on renal resistance. The 23 amino acid peptide (the phenylalanine-arginine C terminal extension of atriopeptin I), designated atriopeptin II, was natriuretic and spasmolytic (in vitro) on both intestinal and vascular strips and was a potent renal vasodilator in vivo. Thus, the renal vasodilator activity present in cardiac atrial extracts appears to derive from a proteolytic process which selectively generates the 23 amino acid peptide, atriopeptin II. Further cleavage with the loss of phenylalanine-arginine C-terminal, as occurs with atriopeptin I, markedly suppresses the renal vasodilation.
Effect of right ventricular pressure on the end-diastolic left ventricular pressure-volume relationship before and after chronic right ventricular pressure overload in dogs without pericardia.
Authors: Little W C , Badke F R , O'Rourke R A
Published: June 2012

We studied the effect of chronic right ventricular pressure overload on diastolic ventricular interdependence in dogs without pericardia, instrumented to measure left ventricular pressure, right ventricular pressure, and 3 left ventricular dimensions. We studied 12 dogs before (control) and nine dogs after 6 weeks of pulmonary artery constriction producing systolic right ventricular pressure greater than or equal to 70 mm Hg. Compared to control, following pulmonary artery band there was greater (P less than 0.01) interventricular septal mass (53 +/- 15 vs. 35 +/- 7 mg, mean +/- SD), thickness (15 +/- 2 vs. 10 +/- 1 mm), and ratio of the surface area of the interventricular septal to total left ventricular surface area (0.38 +/- 0.03 vs. 0.33 +/- 0.02), but unchanged left ventricular free wall mass (81 +/- 12 vs. 84 +/- 14 mg) and thickness (11 +/- 2 vs. 11 +/- 2 mm). End-diastolic right and left ventricular pressures and left ventricular volume were varied by vena cava and pulmonary artery occlusions and releases. Volume was calculated as an ellipsoid and the data in each dog fit to: left ventricular pressure = a0 + a1V + a2V2 + a3V3 + a4V4 + bPRV, r greater than or equal to 0.91 in each dog. During control, b was similar, whether calculated from both pulmonary artery and vena cava occlusions (0.47 +/- 0.09) or from vena cava occlusions alone (0.43 +/- 0.11), and was greater than the ratio of the interventricular septal surface area to left ventricular surface area (0.33 +/- 0.02, P less than 0.05). Following the pulmonary artery band, b decreased to 0.21 +/- 0.10 (P less than 0.05) and was less than the ratio of interventricular septal surface area to the left ventricular surface area which increased to 0.38 +/- 0.03 (P less than 0.05). We conclude that the effect of alterations in right ventricular pressure on the end-diastolic left ventricular pressure volume relationship, independent of the pericardium, is reduced following the pulmonary artery band that produces interventricular septal hypertrophy. These results are consistent with the hypothesis that the effect of alterations of right ventricular pressure on the diastolic left ventricular pressure-volume relationship depends on the relative elastance of the interventricular septum and left ventricular free wall, and not simply on the ratio of the interventricular septal surface area to the left ventricular surface area.
Mechanical properties of resting and active isolated coronary arteries.
Authors: De Mey J G , Brutsaert D L
Published: June 2012

Coronary arterial smooth muscle is myogenically active, is acted upon by a variety of modulating agents, and is subjected, in situ, to compression and distension by the myocardium. Its mechanical properties thus play a key role in the regulation of coronary blood flow. To describe these, we applied phase-plane analysis of shortening velocity vs. length and load clamping to strips of isolated coronary arteries made to contract by an increase in extracellular potassium concentration. At any load, length was larger in relaxed than in "resting" preparations. In addition, preloaded shortening was smaller than would be expected from the relation between active isometric force and muscle length. These suggest the occurrence of stretch-activation and shortening-inactivation. To judge from both phase-plane analysis and quick release experiments, shortening velocity depended on load as well as on time. Velocity decreased with increasing duration of contraction. Shortened coronary arteries resisted lengthening induced by loading and could transiently bear loads that considerably exceeded isometric force. This load-bearing capacity increased with increasing shortening. In conclusion, coronary arterial smooth muscle displays the classical relationship between length, force, and velocity. However, the nature of this relationship changes with duration of activity. In addition, it is greatly affected during changes in length or load, such as expected when the arterial wall is exposed to pulsatile blood flow and is surrounded by mechanically active muscle.
Effects of growth in low potassium medium or ouabain on membrane Na,K-ATPase, cation transport, and contractility in cultured chick heart cells.
Authors: Kim D , Marsh J D , Barry W H , Smith T W
Published: June 2012

Growth of cultured cells in low potassium medium has been shown to result in an increase in the number of Na,K-ATPase sites. This phenomenon and its physiological and pharmacological consequences were examined in spontaneously beating monolayers of cultured chick heart cells. Growth of cells in 1 mM extracellular potassium, 2 microM ouabain, or 1 microM veratridine for 48 hours caused 60%, 40%, or 20% increases, respectively, in the total number of specific ouabain binding sites measurable in intact cells. Acute exposure of control cells grown in 4 mM to 1 mM extracellular potassium caused elevation of steady state [Na+]i by 37%, while 1 microM veratridine exposure increased [Na+]i by 12%. After 48 hours of growth in 1 mM extracellular potassium, intracellular sodium concentrations declined to near-control levels. In cells grown in low extracellular potassium and then equilibrated with 4 mM potassium for 30 minutes, the positive inotropic effects of 1 mM extracellular potassium and 0.3 microM isoproterenol, expressed as a percent of contractile response to 3.6 mM calcium, were 40 +/- 6% and 37 +/- 5% (means +/- SEM), respectively, in low potassium-grown cells, compared with 63 +/- 8% and 35 +/- 4% in control cells. Growth of cells in low potassium shifted the concentration-effect curve for ouabain to the right. The rapid component of calcium uptake in zero extracellular sodium was significantly lower in low potassium-grown cells than in control cells after equilibration in 1 mM extracellular potassium for 30 minutes. These findings demonstrate that prolonged exposure of cultured heart cells to 1 mM extracellular potassium or ouabain causes induction of additional functional sarcolemmal sodium pump sites. The increased levels of intracellular sodium caused by these interventions appear to be an important determinant of sodium pump site density. The reduced contractile response of cells grown in 1 mM extracellular potassium and ouabain (but not isoproterenol) supports the view that elevated intracellular sodium due to Na,K-ATPase inhibition mediates the positive inotropic response to low extracellular potassium and ouabain, probably via augmented transsarcolemmal sodium-calcium exchange. In addition, our results support a mechanism of inotropic action of digitalis glycosides based on inhibition of the sodium pump rather than altered calcium binding properties of sarcolemmal sites due to cardiac glycoside binding to Na,K-ATPase.
Length dependence of activation studied in the isovolumic blood-perfused dog heart.
Authors: Tucci P J , Bregagnollo E A , Spadaro J , Cicogna A C , Ribeiro M C
Published: June 2012

In studies utilizing the isolated isovolumic blood-perfused canine heart, left ventricular pressure was measured following a sudden expansion of ventricular volume. An increase in performance occurred in two phases: first, there was an instantaneous rise of developed pressure simultaneous with ventricular distension; in the second phase, developed pressure continued to increase for several minutes until a final steady state was reached. The immediate increase in developed pressure occurred with a prolongation of the time-to-peak pressure, and there was no further change of time-to-peak pressure during the time-dependent increase of developed pressure. In another series of experiments, systolic pressure was elevated without changing resting volume, and mechanical performance changed in a different manner: after an increase in systolic load, there was a modest and transient decrease of developed pressure; thereafter, ventricular pressure recovered only to original values. The influence of different degrees of ventricular expansion, calcium, and verapamil were studied. Under higher ventricular dilations the immediate as well as the slow increase of contraction were heightened and the time to reach half of the slow increase was shortened. When ventricular dilation was induced during an infusion of calcium chloride, higher values for the immediate pressure increase were observed, whereas the time-dependent increase and the time to reach half of the slow increase did not change in comparison with control studies. Verapamil decreased the immediate and the time-dependent enhancement of contraction. The time-dependent increase in developed pressure occurs more slowly with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of myocardial and vascular alpha-adrenergic receptor affinity. Effects of guanine nucleotides, cations, estrogen, and catecholamine depletion.
Authors: Colucci W S , Gimbrone M A , Alexander R W
Published: June 2012

The threshold sensitivity of cardiovascular tissues to alpha-adrenergic stimulation is determined largely by the affinity of alpha-adrenergic receptors for agonists. To determine whether changes in alpha-adrenergic receptor affinity could contribute to the regulation of cardiac and vascular responsiveness, we used the alpha-adrenergic-selective radioligands, [3H]prazosin, [3H]-WB-4101, and [3H]rauwalscine, to study and contrast the determinants of alpha-adrenergic receptor affinity in myocardium and vascular smooth muscle from the rat. In both tissues, l-epinephrine binding to the alpha 1-adrenergic receptor describes a shallow curve suggesting more than one affinity state. Computer analysis of binding to myocardial alpha 1-receptors indicates that 15% are of high affinity (Kd = 11 nM) and 85% are of low affinity (Kd = 400 nM). Expression of high affinity sites is magnesium dependent (maximum effect, 5-10 mM), and suppressed by the guanosine 5'-triphosphate analogue Gpp(NH)p (maximum effect, 1 mM) and sodium (maximum effect, 100-200 mM). In vascular smooth muscle, agonist-binding curves are also shallow and exhibit a similar response to that of Gpp(NH)p. Basal receptor affinity in myocardium is significantly higher (5.4-fold) than in vascular smooth muscle. Unlike vascular smooth muscle, in which alpha 1-adrenergic receptor affinity is increased by estrogen or reserpine treatment of the animal, the receptor in myocardium is unaffected by these treatments. In vascular smooth muscle, following reserpine-induced increase in alpha-adrenergic receptor affinity, the Gpp(NH)p effect is still present. Thus, alpha 1-adrenergic receptors in both myocardium and vascular smooth muscle exist in two affinity states and are subject to regulation by several factors, including guanine nucleotides, mono- and divalent cations, tissue of origin, sex hormones, and the level of sympathetic stimulation. Potentially, alterations in alpha 1-adrenergic receptor affinity, independent of a change in receptor number, may play an important role in the regulation of cardiovascular tissue responsiveness to catecholamines.
A mathematical model of the effects of acetylcholine pulses on sinoatrial pacemaker activity.
Authors: Michaels D C , Matyas E P , Jalife J
Published: June 2012

A mathematical model of dynamic vagus-sinus interactions was devised based on Hodgkin and Huxley-type equations of time- and voltage-dependent membrane currents. Brief vagal pulses were modeled with a concentration-dependent, acetylcholine-activated, potassium current. Single acetylcholine ("vagal") pulses scanning the sinus cycle induced changes in pacemaker rhythm that depended on pulse magnitude, duration, and time of occurrence during the cycle. Phase-response curves summarizing these effects are strikingly similar to experimental results. Notably, appropriately timed acetylcholine pulses could produce an acceleratory response. With repetitive acetylcholine input, the model produced various patterns of synchronization of the sinus pacemaker. There was stable entrainment at harmonic (i.e., 1:1, 2:1, etc.) relations, as well as more complex arrhythmic patterns that depended on the relationship between the acetylcholine cycle length and the sinus pacemaker period. In some cases, shortening of the acetylcholine input cycle length led to "paradoxical" acceleration of the sinus pacemaker. Simulations suggest that many clinically observed sinus rhythm disturbances can be explained by dynamic vagus-sinus interactions.
Calcium, sodium, and the calcium paradox.
Authors: Nayler W G , Perry S E , Elz J S , Daly M J
Published: June 2012

The effect of "sodium loading," of verapamil and of nifedipine on the gain in calcium and sodium, and on the loss of myoglobin, during the calcium paradox in adult rat hearts was examined. Raising cell sodium from 56.5 +/- 2.6 to 129.5 +/- 10.2 mumol sodium/gram dry weight did not alter the degree or rate of calcium gain or myoglobin release during calcium repletion after long periods (greater than 2 minutes) of calcium-free perfusion; under these conditions, and in the presence of 10 micrograms/liter verapamil, calcium gain was enhanced. However, after shorter periods (0.5-1.5 minutes), of calcium-free perfusion, calcium gain was enhanced in "sodium-loaded" hearts, even in the absence of verapamil, and particularly during the early stages of repletion. The presence of 1 and 10 mumol/liter dl-verapamil and 1 mumol/liter nifedipine before, during, and after 10 minutes of calcium-free perfusion significantly (P less than 0.01) slowed the early (up to 1 minute for verapamil and 2 minutes for nifedipine) but not the late gain in calcium. When verapamil was present, the late gain in calcium was actually enhanced. These agents also abolished the early (45 seconds) but not the late (greater than 2 minutes) gain in sodium that occurs during repletion. We propose that the gain in calcium that occurs during calcium repletion after a period of calcium-free perfusion can be divided into at least two phases (early and late), and that the early phase contains a verapamil/nifedipine-sensitive component and a verapamil/nifedipine-insensitive component, the latter probably involving sodium-calcium exchange.
Effects of chronic hypertension and sympathetic nerves on the cerebral microvasculature of stroke-prone spontaneously hypertensive rats.
Authors: Werber A H , Heistad D D
Published: June 2012

The purpose of this study was to examine hemodynamic mechanisms which protect cerebral vessels against chronic hypertension, and contribute to protective effects of sympathetic nerves in the cerebral circulation. We studied stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. At 3-4 weeks of age, all rats underwent removal of one superior cervical sympathetic ganglion. Approximately 1 year later, we cut the superior cervical sympathetic nerve contralateral to the chronic ganglionectomy and exposed pial arterioles on the cerebral cortex ipsilateral or contralateral to the chronic ganglionectomy. We measured aortic, pial arteriolar, and venous pressures with a servo-null technique, and cerebral blood flow with microspheres. Large artery resistance and small vessel resistance were calculated. During control conditions, pressure in pial arterioles was higher in stroke-prone spontaneously hypertensive rats (83 +/- 6 mm Hg) (mean +/- SE) than in Wistar-Kyoto rats (60 +/- 3 mm Hg, P less than 0.05), even though large artery resistance was almost two-fold greater in stroke-prone spontaneously hypertensive rats than in Wistar-Kyoto rats (P less than 0.05). During maximal dilation produced by seizures, large artery resistance was almost three-fold higher in stroke-prone spontaneously hypertensive rats than in Wistar-Kyoto rats (P less than 0.05). Small vessel resistance also was increased in stroke-prone spontaneously hypertensive rats. During seizures in stroke-prone spontaneously hypertensive rats, large artery resistance was 29% lower in chronically denervated vessels than in acutely denervated vessels (P less than 0.05). Three stroke-prone spontaneously hypertensive rats had pial vessels with a "sausage string" appearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered cerebral vessel innervation in the spontaneously hypertensive rat.
Authors: Lee T J , Saito A
Published: June 2012

Autonomic innervation in the cerebral arterial walls of adult male spontaneously hypertensive rats and of normotensive Wistar-Kyoto rats was studied. When examined by fluorescence microscopy, dense catecholamine fluorescence was observed in anterior cerebral and middle cerebral arteries of both Wistar-Kyoto and spontaneously hypertensive rats. However, vertebral and basilar arteries and small pial arteries of Wistar-Kyoto rats received extremely sparse or no catecholamine fluorescence, whereas, in the respective regions of spontaneously hypertensive rats, catecholamine fluorescence was found to be significantly elevated. The endogenous norepinephrine content was also higher in cerebral arteries of spontaneously hypertensive than of Wistar-Kyoto rats. When examined ultrastructurally (potassium permanganate fixation), the incidence of granular vesicle-containing nerves, indicative of sympathetic nerves, was found to be significantly elevated in all cerebral arteries of spontaneously hypertensive rats examined. In contrast, the agranular vesicle-containing nerve, indicative of nonsympathetic nerves, with close synaptic cleft distance (less than 2 micron) was found to decrease or remain unchanged in the cerebral arteries of spontaneously hypertensive rats. These results suggest that cerebral sympathetic vasoconstriction may become more prominent than nonsympathetic vasodilation in spontaneously hypertensive rats. This finding lends further credence to the previous in vivo findings that cerebral sympathetic vasoconstrictor nerves become more functional and exhibit a protective effect against brain lesions during hypertension. The potential roles of neurogenic components involved in cerebral blood flow autoregulation are also discussed.
The role of vasopressin and the sympathetic nervous system in the cardiovascular response to vagal cold block in the conscious dog.
Authors: Hasser E M , Haywood J R , Johnson A K , Bishop V S
Published: June 2012

This study examined the role of arginine vasopressin in the pressor response to vagal cold block and evaluated a possible interaction between vasopressin and the sympathetic nervous system during vagal block in conscious dogs with (carotid sinus intact) and without (sinoaortic denervated) functional arterial baroreflexes. In both carotid sinus intact and sinoaortic denervated dogs, elimination of the arginine vasopressin pressor system by the specific vasopressin antagonist d(CH2)5Tyr(Me)AVP did not alter the response to vagal block, as evaluated by changes in arterial pressure. Subsequent removal of the sympathetic nervous system by ganglionic blockade abolished the response to vagal block. When ganglionic blockade was induced in the absence of the vasopressin antagonist, the pressor response to vagal block was reduced by only 60%. Arginine vasopressin antagonist after ganglionic blockade reduced the response to vagal block by an amount equivalent to 45% of the original increase in pressure. The effects of blockade of either vasopressin or the sympathetic nervous system on the pressor response to vagal block were significantly greater when the other system had previously been eliminated. Data suggest that both arginine vasopressin and the sympathetic nervous system contribute to the pressor response to vagal block. One interpretation of these results is that vasopressin also interacts centrally to inhibit sympathetic outflow and thus modulates the hemodynamic manifestation of interruption of vagal afferents.
Mechanisms of adenosine triphosphate-, thrombin-, and trypsin-induced relaxation of rat thoracic aorta.
Authors: Rapoport R M , Draznin M B , Murad F
Published: June 2012

The mechanisms by which adenosine triphosphate, thrombin, and trypsin cause relaxation of vascular smooth muscle were investigated. Relaxation of the rat thoracic aorta with adenosine triphosphate, thrombin, and/or trypsin was associated with increased levels of cyclic guanosine monophosphate in both time- and concentration-dependent manners. Thrombin and trypsin did not alter cyclic adenosine monophosphate levels, whereas adenosine triphosphate increased cyclic adenosine monophosphate levels after significant relaxation occurred. Removal of the endothelium abolished adenosine triphosphate-, thrombin-, and trypsin-induced relaxation and the associated increased levels of cyclic nucleotides. Relaxation due to these agents was also inhibited by exposure to nordihydroguaiaretic acid, a lipoxygenase inhibitor, and eicosatetraynoic acid, a lipoxygenase and cyclooxygenase inhibitor. Indomethacin, a cyclooxygenase inhibitor, potentiated relaxation to these agents, whereas the increased levels of cyclic nucleotides due to adenosine triphosphate were unaltered. Bromophenacyl bromide, a phospholipase A2 inhibitor, decreased relaxation due to adenosine triphosphate, thrombin, and trypsin and the associated increased levels of cyclic nucleotides. Removal of extracellular calcium, which also presumably inhibits phospholipase A2, prevented the elevated levels of cyclic nucleotides and the inhibitory effects of adenosine triphosphate and trypsin on contraction. In contrast, sodium nitroprusside-induced relaxation and/or increased levels of cyclic guanosine monophosphate were unaltered by nordihydroguaiaretic acid, eicosatetraynoic acid, bromophenacyl bromide, and removal of extracellular calcium. After incubation of intact tissue with 32P-orthophosphate, the patterns of protein phosphorylation caused by adenosine triphosphate, thrombin, and trypsin were indistinguishable from those of acetylcholine, sodium nitroprusside and 8-bromo cyclic guanosine monophosphate. All these agents dephosphorylated myosin light chain. Thus, the present study supports the hypothesis that relaxation induced by adenosine triphosphate, thrombin, and trypsin is mediated through the formation of an endothelial factor which elevates cyclic guanosine monophosphate levels and causes cyclic guanosine monophosphate-dependent protein phosphorylation and dephosphorylation of myosin light chain.
Hemodynamic and microvascular responses in the hindquarters during the development of renal hypertension in rats. Evidence for the involvement of an autoregulatory component.
Authors: Meininger G A , Lubrano V M , Granger H J
Published: June 2012

Microvascular responses in the cremaster muscle were compared with changes in mean arterial pressure and hindquarters vascular resistance during the development (initial 3 hours) of two-kidney one-clip renal hypertension in rats, to examine the possibility that an autoregulatory mechanism may contribute to the development of hypertension. Rats were anesthetized with urethane and chloralose and implanted with Doppler flow probes on the renal artery and abdominal aorta. Acute hypertension was produced by inflation of a balloon occluder on the renal artery to reduce renal flow by 50%. The cremaster muscle was isolated with intact innervation and circulation for measurement of microvessel diameters. To determine whether increased pressure contributed to the changes in hindquarters vascular resistance or in microvascular diameters during acute hypertension, arterial pressure was prevented from increasing in the hindquarters region after renal artery stenosis by servo-controlled inflation of a balloon occluder around the sacral aorta to maintain hindquarters pressure at normotensive levels. In hypertensive rats with unprotected hindquarters, mean arterial pressure and hindquarters vascular resistance increased 26% and 20%, respectively, after renal artery stenosis. In comparison, hypertensive rats with protected hindquarters exhibited a similar increase in mean arterial pressure, but hindquarters vascular resistance was significantly reduced compared to that in hypertensive rats with unprotected hindquarters. In the cremaster microcirculation, vasoconstriction was observed only in the small third- (mean +/- SEM: 29 +/- 4 micron) and fourth- (12 +/- 2 micron) order arterioles in rats with unprotected hindquarters. In general, microvessel diameters in rats with protected hindquarters that had lower hindquarters vascular resistance than those with unprotected hindquarters were larger for the second- (82 +/- 5 micron), third-, and fourth-order arterioles, suggesting less vasoconstrictor tone. Our data indicate that the increase in hindquarters resistance during the development of renal hypertension is, in part, dependent on the presence of a pressure-dependent autoregulatory process.
Altered control of hindlimb vascular resistance by vagal afferents in spontaneously hypertensive rats. Difference in the early and late stage of hypertension.
Authors: Hoka S , Takeshita A , Yamamoto K , Ito N , Ashihara T , Nakamura M
Published: June 2012

The aim of this study was to examine whether control of vascular resistance by vagal afferents is altered in the early as well as late stage of hypertension. We examined the effects of vagotomy on hindlimb vascular resistance as well as on arterial baroreflex control of hindlimb vascular resistance in spontaneously hypertensive rats and Wistar-Kyoto rats, 12 and 35 weeks old. Vagotomy in rats with the intact arterial baroreceptors increased hindlimb vascular resistance in all four groups. Hindlimb vascular responses to graded sympathetic nerve stimulation were closely linear up to 6 Hz in all groups, and the slope of the response was approximately 1.4 times steeper in spontaneously hypertensive than in Wistar-Kyoto rats, in both the young and old groups. The increase in hindlimb vascular resistance after vagotomy normalized by the slope of the response to sympathetic nerve stimulation was greater in young spontaneously hypertensive rats than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive rats than in old Wistar-Kyoto rats. Vagotomy increased the gain of arterial baroreflex control of hindlimb vascular resistance in young spontaneously hypertensive rats, and in two groups of Wistar-Kyoto rats, but not in old spontaneously hypertensive rats. The percent increase in the gain of arterial baroreflex control of hindlimb vascular resistance after vagotomy tended to be greater in young spontaneously hypertensive than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. Central venous pressure and left ventricular end-diastolic pressure were higher in spontaneously hypertensive than in Wistar-Kyoto rats in both young and old groups. Left atrial distensibility assessed by obtaining the atrial pressure-volume relationship was comparable between young spontaneously hypertensive and young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. These results indicate that vagal afferents exert tonic inhibition on control of hindlimb vascular resistance in spontaneously hypertensive as well as in Wistar-Kyoto rats, and that tonic inhibitory influence of vagal afferents on control of hindlimb vascular resistance is altered in spontaneously hypertensive rats, augmented in young, but attenuated in old, spontaneously hypertensive rats, compared with that in age-matched Wistar-Kyoto rats. It is considered that altered control of vascular resistance by vagal afferents in spontaneously hypertensive rats may result from changes in vagal afferent activity.
The vasopressor response to centrally administered ouabain.
Authors: Caldwell R W , Songu-Mize E , Bealer S L
Published: June 2012

Ouabain (80 micrograms/kg) injected into the lateral cerebroventricles (ICV) of rats produced a prompt and sustained increase in arterial blood pressure. A diastolic blood pressure increase of about 40 mm Hg began within 10 minutes of injection and lasted at lest 1 hour. This dose of ouabain had no effect on arterial pressure when given intravenously. The vasopressor response to intracerebroventricularly administered ouabain was not blocked by prior intravenous administration of phentolamine (1 mg/kg) or hexamethonium (3 mg/kg). However, continuous intravenous infusion of saralasin (2 micrograms/kg per min) prevented the pressor response to intracerebroventricularly administered ouabain. In addition, bilateral nephrectomy, adrenalectomy, pretreatment with intravenously administered propranolol (2 mg/kg) or captopril (10 mg/kg) abolished the increase in blood pressure evoked by intracerebroventricularly administered ouabain. Plasma renin and epinephrine levels at the peak of the pressor response to intracerebroventricularly administered ouabain were respectively, about 2.5- and 2-fold higher than in control rats. Our data indicate that ouabain administered into the central nervous system produces a hypertensive effect which does not primarily involve peripheral alpha-adrenergic receptors, but appears to be due to angiotensin II produced by renin of renal origin. These data suggest that digitalis agents can interact with sites in the central nervous system to induce a release of renin from the kidney; this release appears to involve activation of beta-adrenergic receptors by catecholamines from the adrenal medulla, perhaps through a direct adrenal-kidney vascular network.
Effects of pericardial effusates of various conductivities on body-surface potentials in dogs. Documentation of the eccentric spheres model.
Authors: Kramer D A , Hamlin R L , Weed H R
Published: June 2012

The purpose of this study was to discover the cause and magnitude of changes in the body-surface potentials occurring when: (1) fluids of various conductivity were added to the pericardial sac, or (2) the volume of the blood within chambers of the heart was either increased or decreased. Fluids added to the pericardium were physiological saline, whole-blood, and mineral oil. Magnitudes of body-surface potentials were compared to the predictions based on a mathematical eccentric spheres model of the heart and torso developed previously by Rudy and Plonsey. Data demonstrated conclusively that there is a nonlinear relationship between the body-surface potentials and the conductivity of the pericardial layer. This relationship is one in which the body-surface potentials of the anterior chest were found to decrease when conductivity of the pericardial layer was either increased or decreased. These changes in body-surface potentials were caused solely by alterations in the conductivity and volume of the fluid effusate. It was demonstrated that these changes were not caused by any "stretching" or "compression" of the cardiac tissue caused by the altered fluid volumes in and around the heart. Findings were accurately predicted by the eccentric spheres model, thereby confirming the model's usefulness as a predictive instrument. The model provides an explanation for the nonlinear relationship that was exhibited by the data.