Biomedical subjects

S F Vatner

Publications and source records attributed to S F Vatner.

At least 127 records · Page 7Linked to original sources

PubMed1989

Species differences in regulation of alpha-adrenergic receptor function.

The effects of alpha-adrenergic receptor stimulation with norepinephrine and phenylephrine after beta-adrenergic and muscarinic receptor blockades were compared in conscious baboons, calves, dogs, and rats in which left ventricular (LV) pressure. LV maximum rate of pressure development (dP/dt), and heart rate were measured. Autonomic receptor density was examined in crude sarcolemmal preparations from the hearts. The major physiological differences were observed in rats, where alpha 1-adrenergic receptor stimulation resulted in the greatest (P less than 0.05) increases in LV dP/dt (29 +/- 2%) in response to phenylephrine, 5.0 micrograms/kg, in comparison with responses in dogs (12 +/- 4%), calves (3 +/- 3%), and baboons (1 +/- 2%). This was associated with the greatest (P less than 0.05) alpha 1-adrenergic receptor density in the rat heart (73 +/- 5 fmol/mg) compared with values in the baboon (6 +/- 1 fmol/mg), calf (21 +/- 3 fmol/mg), or dog (10 +/- 3 fmol/mg) myocardium. Thus there are major differences among mammalian species in alpha-adrenergic receptor density and physiological responsiveness to alpha-adrenergic agonists.

Adrenergic alpha-Agonists↗

PubMed1989

Natriuretic and diuretic effects of infusion of atrial natriuretic factor in conscious dogs.

We studied the effects of 30-min infusions of the synthetic 25-amino acid atrial natriuretic factor [ANF-(102-126)] and the 28-amino acid ANF-(99-126) at 0.1 and 0.3 micrograms.kg-1.min-1 on urine flow rate, sodium excretion, and arterial pressure in conscious dogs. Each dose was administered on a separate day following a 1-h stabilization period. We also compared the effects of 60-min infusions of ANF, 0.01 micrograms.kg-1.min-1, or water infusion on separate days in conscious dogs. Arterial pressure was reduced in a dose-dependent fashion, reaching statistical significance at a dose of 0.3 micrograms.kg-1.min-1. During the 0.01-micrograms.kg-1.min-1 infusion, the plasma concentration of ANF rose approximately threefold (from 68 +/- 7 to 207 +/- 14 pg/ml), with no change in urine flow rate, sodium excretion, or arterial pressure. At a dose of 0.1 micrograms.kg-1.min-1, urine flow increased (P less than 0.05) by 0.41 +/- 0.15 ml/min, and sodium excretion rose by 72 +/- 24 mu eq/min, but not significantly, whereas plasma ANF levels rose to 1,236 +/- 229 pg/ml. At the highest dose of ANF (0.3 micrograms.kg-1.min-1) urine flow rose by 0.62 +/- 0.16 ml/min, P less than 0.05, and sodium excretion rose by 139 +/- 30 mu eq/min, P less than 0.05, whereas plasma levels of ANF rose to 2,436 +/- 320 pg/ml. In contrast, volume loading with dextran increased urine flow by 3.5 +/- 1.3 ml/min, P less than 0.05, and sodium excretion by 439 +/- 147 mu eq/min, P less than 0.05, whereas ANF rose to only 320 +/- 69 pg/ml. These results suggest that, in the conscious dog, ANF does not cause significant diuretic or natriuretic effects until plasma levels are markedly above those observed in physiological conditions. A possible explanation for the difference between this and previous studies is that the renal effects of ANF, at physiological plasma levels, are indirect and thus dependent on autonomic and hormonal (angiotensin, vasopressin, and aldosterone levels) factors governing the renal function of the animal.

Animals↗

PubMed1989

Superoxide dismutase reduces reperfusion arrhythmias but fails to salvage regional function or myocardium at risk in conscious dogs.

To determine if oxygen free radical scavengers administered before coronary artery reperfusion can limit reperfusion arrhythmias, increase the return of regional function in ischemic myocardium, and reduce tissue necrosis at 1 week after 90-minute coronary artery occlusion and reperfusion, conscious dogs were treated with superoxide dismutase (SOD) and catalase before and for 1 hour after coronary artery reperfusion. Another group was treated with recombinant SOD (rSOD) because the commercially available SOD and catalase contained endotoxin. The conscious dogs were studied 3-4 weeks after implanting left ventricular pressure gauges, ultrasonic wall thickness gauges in the posterior left ventricular wall, left atrial catheters, and arterial catheters, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. The only beneficial effect observed was that the number of arrhythmic beats per minute in the rSOD-treated group was significantly lower (p less than 0.05) when compared with a control group after coronary artery reperfusion. Treatment neither increased the amount of recovery of wall thickening in the ischemic zone nor reduced infarct size when expressed either as a percentage of the area at risk or as a function of collateral blood flow in the ischemic zone. For example, infarct size as a percentage of the area at risk was 32.6 +/- 5.8%, 37.4 +/- 6.4%, 28.3 +/- 5.1% in the control, SOD and catalase-, and rSOD-treated groups, respectively. Thus, although treatment with oxygen free radical scavengers invoked a transient reduction in the number of reperfusion arrhythmias, this treatment in conscious dogs failed to improve regional myocardial dysfunction or reduce the amount of necrosis when compared with a control group. The lack of a sustained salutary effect may indicate that longer periods of treatment with free radical scavengers are required in chronic preparations.

Animals↗

PubMed1989

Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure.

The effects of isoproterenol were examined in 10 conscious, chronically instrumented adult dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by aortic banding at 8-10 weeks of age (LV free wall plus septum-to-body weight ratio, 8.6 +/- 0.5 g/kg) and also in eight control dogs (LV free wall plus septum-to-body weight ratio, 5.1 +/- 0.3 g/kg). Baseline values of heart rate, LV end-diastolic pressure, LV end-diastolic stress, and LV systolic wall stress were greater in the LV failure dogs (p less than 0.01), whereas the ejection phase index, rate of change of LV short-axis diameter, LV dD/dt, was depressed compared with control animals. In the control animals, isoproterenol infusion increased Vcf and LV dD/dt significantly (p less than 0.05), whereas LV systolic wall stress did not change. In the LV failure dogs, the increases in Vcf and LV dD/dt were less (p less than 0.01), and LV systolic wall stress increased (p less than 0.01). In the control animals, LV end-diastolic pressure, LV end-diastolic stress, LV end-diastolic stress-dimension ratio, diastolic radial myocardial stiffness, and the time constant of isovolumic relaxation decreased (p less than 0.05), whereas in the LV failure dogs, LV end-diastolic pressure, LV end-diastolic stress, diastolic radial myocardial stiffness, and the LV end-diastolic stress-dimension ratio increased. In the LV failure group, the endocardial to epicardial blood flow ratio fell to 0.59 +/- 0.06 during isoproterenol infusion, that is, significantly lower than in control dogs (0.93 +/- 0.06). These data support the concept that potent sympathomimetic amines exert deleterious effects on systolic and diastolic function in the failing heart, potentially related to subendocardial hypoperfusion.

Animals↗

PubMed1989

Effects of renin inhibition in the conscious primate Macaca fascicularis.

Pro-His-Pro-Phe-His-Statine-Ile-Phe-NH2 (R-Pep-27), a potent renin inhibitory peptide, was infused into the conscious, sodium-depleted Macaca fascicularis at doses of 0, 0.1, 1, 4, 16, and 32 micrograms/kg/min for 10 minutes. At all doses greater than 0.1 microgram/kg/min, there was a parallel decrease in mean arterial pressure (MAP), plasma renin activity, and plasma angiotensin II (Ang II) concentration. On the other hand, assays with monoclonal antibodies specific for total renin and active renin demonstrated that the peptide's inhibition of circulating active renin stimulated the release of both. The maximal effective R-Pep-27 dose was approximately 16 micrograms/kg/min, which reduced MAP by an average of 15.8 +/- 1.4 mm Hg (n = 14) and plasma renin activity and plasma Ang II concentration to 3% (n = 9) and 15% (n = 5), respectively, of the pretreatment values. At 0.1 microgram/kg/min, there was no significant decrease in MAP; however, measurement of plasma renin activity showed an average decrease in activity of 42% (n = 3). No significant change in the heart rate was observed at all the doses studied. For comparison, intravenous captopril (400 micrograms/kg bolus) was administered after the MAP of the monkeys had recovered from the peptide experiments, and it reduced MAP by 25.1 +/- 2.4 mm Hg (n = 10) without significantly changing plasma renin activity. As anticipated, injection of angiotensin I (80-160 ng/kg bolus) into sodium-depleted monkeys during peptide infusion caused a transient rise in MAP of 14.8 +/- 5.4 mm Hg (n = 4) above the mean pretreatment value.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMed1989

One hour of myocardial ischemia decreases the activity of the stimulatory guanine-nucleotide regulatory protein Gs.

The effect of 1 hour of myocardial ischemia on the function of the stimulatory guanine-nucleotide-binding protein Gs was examined. This study follows our recent finding that myocardial ischemia increases the density of beta-adrenoreceptors in a conscious canine model while having the opposite effect on the activity of adenylate cyclase. Coronary artery occlusion was induced in five conscious dogs and verified by measurement of blood flow using the Doppler and microsphere techniques. Alterations in the level and function of Gs were examined in sarcolemmal membranes prepared from ischemic and nonischemic regions of the left ventricle. After 1 hour of coronary artery occlusion, the functional activity of sarcolemmal Gs, as determined by reconstitution with cyc- membranes, decreased by 27 +/- 7% in the ischemic zone. Cholera toxin labeling performed in parallel with the reconstitution studies demonstrated a similar decrease of 28 +/- 7%. This was associated with decreases in basal activity and decreases in adenylate cyclase activity stimulated by GTP, GTP plus isoproterenol, sodium fluoride, and forskolin. Thus, a defect distal to the beta-adrenoreceptor occurs in the transduction of adrenergic signals to the heart as a consequence of 1 hour of ischemia.

Adenylyl Cyclases↗

PubMed1989

Subendomyocardial exhaustion of blood flow reserve and increased fibrosis in conscious dogs with heart failure.

The effects of near-maximal coronary vasodilation were examined in conscious dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by either aortic banding alone or aortic banding plus a peripheral arteriovenous shunt. The findings were compared with results in littermates with compensated LV hypertrophy and with a third group of normal dogs. At rest, there was a marked difference in the intramyocardial distribution of coronary flow, measured with radiolabeled microspheres. The endocardial/epicardial (endo/epi) flow ratio in the LV failure dogs was 0.96 +/- 0.08 as compared with control dogs (1.28 +/- 0.06, p less than 0.05) or dogs with compensated LV hypertrophy (1.23 +/- 0.08, p less than 0.05). During near-maximal coronary vasodilation with adenosine, all groups showed similar increases in subepimyocardial (epi) flow. While significant increases in subendomyocardial (endo) flow during adenosine infusion were seen in the control group (0.88 +/- 0.10 to 3.53 +/- 0.24 ml/min/g) and in dogs with compensated LV hypertrophy (1.12 +/- 0.14 to 3.60 +/- 0.16 ml/min/g), there was no change in endo flow in the LV failure dogs (1.55 +/- 0.20 to 1.71 +/- 0.47 ml/min/g) and a further significant reduction in the endo/epi flow ratio was observed (0.30 +/- 0.06, p less than 0.01). These hemodynamic changes were associated with chronic multifocal interstitial or discrete areas of fibrosis observed preferentially in endo layers. Thus, endo flow reserve is nearly exhausted in dogs with decompensated pressure overload LV hypertrophy, which may induced periodic episodes of endo ischemia resulting in myocyte necrosis and fibrosis, which in turn results in exacerbation of LV failure.

Adenosine↗

PubMed1989

Chronic norepinephrine elicits desensitization by uncoupling the beta-receptor.

The goal of this study was to determine the mechanism of beta-adrenergic receptor desensitization after chronic elevation of circulating NE levels. Osmotic minipumps containing either NE or saline were implanted subcutaneously in dogs for 3-4 wk. Physiologic desensitization to isoproterenol was confirmed in conscious dogs, i.e., left ventricular dP/dt increased in response to isoproterenol (0.4 micrograms/kg per min) by 5,625 +/- 731 mmHg/s in control dogs with saline pumps, and significantly less, P less than 0.01, by 2,093 +/- 263 mmHg/s in dogs with NE pumps. Myocardial beta-adrenergic receptor density as determined with 125I-cyanopindolol binding was 49% higher (p less than 0.05) in the NE pump group. However, beta-adrenergic receptor agonist binding with isoproterenol demonstrated a significant shift into the low affinity state for the animals with NE pumps. Basal, GTP plus isoproterenol, 5'-guanylylimidodiphosphate, sodium fluoride, and forskolin-stimulated adenylate cyclase activity in the NE pump group were significantly depressed (P less than 0.05) by amounts ranging from 20 to 40%. The functional activity of the guanine nucleotide binding protein Gs was also reduced (P less than 0.05) in animals with NE pumps. Thus, the process of desensitization in response to chronic elevation of NE levels in intact, normal dogs does not involve a decrease in beta-adrenergic receptor density. Rather, it is characterized by reduced adenylate cyclase activation and uncoupling of the beta-adrenergic receptor in association with decreased activity of the GTP-coupling protein Gs.

Adenylyl Cyclases↗

PubMed1988

Reduced subendocardial myocardial perfusion as one mechanism for congestive heart failure.

One mechanism for the eventual decompensation of the hypertrophied to the failing heart may involve inadequate myocardial perfusion. In support of this concept are studies in experimental models of both right and left ventricular hypertrophy and failure. These studies demonstrate blunted reactive hyperemic responses to brief periods of coronary artery occlusion, and reduced vasodilation in response to adenosine, when the most severe impairment in coronary reserve occurs in the subendocardium. During exercise, in the hypertrophied and failing heart, the normal coronary vasodilator response is also blunted. Although endocardial/epicardial blood flow ratios are depressed in congestive heart failure under baseline conditions, the endocardial/epicardial ratio decreases further with stress, e.g., during either adenosine or reactive hyperemia. These data suggest that one mechanism of failure of the severely hypertrophied heart may involve inadequate coronary perfusion to the subendocardium.

Adenosine↗

PubMed1988

One hour of myocardial ischemia in conscious dogs increases beta-adrenergic receptors, but decreases adenylate cyclase activity.

An increased myocardial beta-adrenergic receptor density has been reported following myocardial ischemia. However, it is not clear whether these receptors are effectively coupled to adenylate cyclase which would be necessary for enhanced physiological responsiveness. We, therefore, examined the effects of myocardial ischemia in six conscious dogs (4 intact and 2 with posterior wall denervation) in which the left circumflex coronary artery was occluded. Ischemia was verified by measurement of regional blood flow by radioactive microspheres. After 1 h of coronary artery occlusion, the dogs were anesthetized with pentobarbital and the left ventricle was divided into normal, intermediate and ischemic regions. A crude membrane fraction was prepared from each region. beta-Adrenergic receptors were quantitated with 125I-cyanopindolol binding and adenylate cyclase activity was measured. In all six animals studied, beta-adrenergic receptor density increased progressively and adenylate cyclase activity decreased progressively, when the ischemic myocardium was compared to the intermediate and the non-ischemic myocardium. Since adenylate cyclase activity declined, these results do not support the concept that the increased beta-receptor density induced by myocardial ischemia is causally related to enhanced beta-adrenergic sensitivity.

Adenylyl Cyclases↗

PubMed1988

Sympathetic activation induces asynchronous contraction in awake dogs with regional denervation.

To determine effects of regional left ventricular (LV) denervation on regional contractile responses to sympathetic activation, dogs with posterior LV wall denervation (posterior wall-denervated group) and dogs with innervated posterior LV walls (intact group) were studied during excitement, exercise, bilateral sympathetic nerve stimulation, and norepinephrine infusion. In intact conscious dogs, all modes of sympathetic activation increased the magnitude and decreased the time of onset of systolic wall thickening (WT) similarly in the anterior and posterior wall. In the denervated group, excitement failed to increase posterior WT during systole but instead elicited asynchronous contraction, i.e., postsystolic WT, as well as delayed onset of contraction. Asynchronous contraction was not observed with excitement after beta-adrenergic receptor blockade. Asynchronous contraction of the posterior wall was also observed during the initial phase of exercise in conscious dogs and during bilateral stellate stimulation in anesthetized dogs in the posterior wall-denervated group. In comparison to neural activation, adrenergic receptor activation with norepinephrine (0.2 microgram/kg-1.min-1 iv) induced a supersensitive increase in systolic WT in the denervated posterior wall (36 +/- 5%) compared with the anterior wall (17 +/- 2%) and a delay in the end of contraction in the anterior region. Thus asynchronous contraction can be elicited in dogs with regional LV denervation as a result of an early and enhanced contraction in the innervated region during neural sympathetic activation. The reverse was observed with systemic administration of norepinephrine because of catecholamine supersensitivity in the denervated posterior wall.

Animals↗

PubMed1988

Responses to coronary artery occlusion in conscious dogs with selective cardiac denervation.

The extent to which cardiac denervation alters responses to myocardial ischemia remains controversial. This study compared responses to 24-h coronary artery occlusion (CAO) on measurements of wall thickness (ultrasonic crystals), regional myocardial blood flow (microspheres), and infarct size (triphenyltetrazolium chloride technique) in three groups of conscious dogs with 1) selective posterior left ventricular (LV) wall denervation, 2) selective ventricular denervation, or in 3) intact dogs. After CAO, hemodynamic changes were not different among the three groups. Wall thickening in the ischemic zone became akinetic or paradoxical early after CAO and did not recover in any group over the 24-h monitoring period. Blood flow in the area at risk fell similarly in all groups. Infarct size, as a percentage of the area at risk, was 45 +/- 7% in intact, 48 +/- 6% in posterior LV wall-denervated, and 48 +/- 8% in ventricular-denervated group. There was, however, a lower (P less than 0.05) frequency of arrhythmic beats per minute after 3 h of CAO in the ventricular-denervated group (3.2 +/- 1.4) compared with the intact (11.3 +/- 4.1) or posterior wall-denervated (12.6 +/- 3.2) group. An additional group of ventricular-denervated dogs was studied to determine the effects of sequential, brief 2-min CAO at 2, 4, and 8 wk after denervation. Responses of regional wall thickening to CAO were not affected significantly even after 8 wk following ventricular denervation. Thus, in conscious dogs, neither selective ventricular denervation nor selective denervation of the posterior LV wall improved collateral blood flow, affected regional function favorably, or reduced infarct size after CAO.

Animals↗

PubMed1988

Alpha-adrenergic vasoconstriction and receptor subtypes in large coronary arteries of calves.

We investigated alpha-adrenoceptor subtype distribution in large coronary arteries from both functional and biochemical perspectives. The effects of intracoronary administration of the selective alpha 1-adrenoceptor agonist phenylephrine (0.1-5.0 micrograms/kg ic), of the selective alpha 2-adrenoceptor agonist B-HT 920 (0.1-5.0 micrograms/kg ic), and of the mixed alpha 1 + 2-adrenoceptor agonist norepinephrine (0.01-0.5 micrograms/kg ic) were examined on measurements of left circumflex coronary artery diameter in conscious calves. After beta-adrenergic blockade, equivalent reductions in large coronary artery diameter were observed with phenylephrine (-6.9 +/- 0.7%), B-HT (-5.9 +/- 0.5%), and norepinephrine (-6.0 +/- 0.4%). Phenylephrine-induced constrictions were abolished by prazosin, an alpha 1-selective antagonist, but unaffected by rauwolscine, an alpha 2-selective antagonist. Conversely, the B-HT-induced constriction was abolished by rauwolscine but unaffected by prazosin. Coronary constriction with norepinephrine was attenuated with either prazosin or rauwolscine and abolished by the two antagonists combined. Ligand-binding studies in which [3H]prazosin and [3H]rauwolscine and sarcolemmal membranes were used revealed an alpha 1-adrenoceptor density of 15 +/- 3.1 fmol/mg protein with a dissociation constant (KD) of 0.7 +/- 0.2 nM and an alpha 2-adrenoceptor density of 68 +/- 5.1 fmol/mg protein, with a KD of 7.4 +/- 1.2 nM. Thus large coronary arteries of the calf contain both alpha 1- and alpha 2-adrenoceptor subtypes, each of which elicits constriction of the large coronary artery in the conscious animal.

Adrenergic alpha-Agonists↗

PubMed1988

Sympathetic augmentation of cardiac function in developing hypertension in conscious dogs.

To determine the alterations in left ventricular (LV) function and the mechanisms involved that occur during the development of perinephritic hypertension, dogs were instrumented with a miniature LV pressure transducer, aortic and left atrial catheters, and ultrasonic crystals to measure LV diameter in the short and long axes and wall thickness. At 2 wk after initiation of perinephritic hypertension, increases (P less than 0.05) were observed in LV systolic pressure, LV end-diastolic pressure, both short- and long-axis end-diastolic diameters, calculated LV end-diastolic volume, stroke volume, global average LV systolic wall stress, first derivative of LV pressure (LV dP/dt), and ejection fraction, whereas mean velocity of circumferential fiber shortening (Vcf) and rate of change of LV short-axis diameter (LV dD/dt) rose but not significantly. At three levels of matched preload and afterload induced by the administration of graded doses of phenylephrine, Vcf, LV dD/dt, and LV dP/dt increased in hypertension compared with the same levels of preload and afterload before hypertension. When the loading conditions in the normotensive and hypertensive dogs were matched, either after ganglionic blockade or beta-adrenergic blockade, both isovolumic and ejection-phase indexes of LV function remained similar before and after hypertension. Thus we conclude that 1) LV function in intact, conscious dogs with early hypertension is enhanced, and 2) the major mechanism for the increase in LV function involves the sympathetic nervous system.

Animals↗

PubMed1988

Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and extent of infarction following reperfusion in conscious baboons.

Two groups of chronically instrumented, conscious baboons were studied. The effects of coronary artery occlusion for 3 hours and reperfusion for 1 week were examined on measurements of left ventricular function, ischemic-zone wall thickness, regional myocardial blood flow, arrhythmias, and extent of necrosis. The experimental group of animals (n = 7) was treated with the calcium channel blocker nisoldipine (0.1 microgram/kg/min) from 1 hour after coronary occlusion to 3 hours after coronary reperfusion. The control group (n = 6) received the vehicle (n = 4) or saline (n = 2). The effects of coronary artery occlusion and reperfusion on arterial pressure, left ventricular systolic pressure, heart rate, and left ventricular dP/dt were similar in both groups. Systolic wall thickening was reversed to paradoxical wall thinning during occlusion in both groups, and there was no recovery to systolic wall thickening over the 1-week period in either group. There were differences in regional blood flow; during coronary artery occlusion, nisoldipine increased blood flow significantly in the endocardium and epicardium of nonischemic and ischemic zones. There was a major difference in the number of arrhythmic beats per minute on reperfusion; during reperfusion, the number of arrhythmias rose markedly in the vehicle-treated group but actually fell in the nisoldipine-treated group. The size of areas at risk, infarcts, infarcts related to the area at risk, and amount of total creatine kinase (CK) and MB-CK appearing in blood were not significantly different in the two groups. Thus, in the conscious baboon, nisoldipine administered 1 hour after coronary artery occlusion exerted a marked effect in diminishing reperfusion-induced arrhythmias and improved blood flow to the ischemic zone during occlusion but did not salvage ischemic tissue.

Animals↗

PubMed1988

Systolic and diastolic dysfunction during atrial pacing in conscious dogs with left ventricular hypertrophy.

To determine the extent to which the hypertrophied left ventricle responds to the chronotropic stress induced by graded atrial pacing rates, we studied conscious, chronically instrumented dogs with severe compensated pressure overload left ventricular (LV) hypertrophy induced by aortic banding in puppies 8-10 weeks of age. At 1-2 years, dogs with severe LV hypertrophy (LV free wall/body wt ratio 6.8 +/- 0.6 g/kg) and sham-operated littermates (LV free wall/body wt ratio 4.0 +/- 0.3 g/kg) were instrumented with ultrasonic dimension crystals to measure LV short axis internal diameter and wall thickness, miniature LV pressure transducers, and aortic and LV catheters. During atrial pacing (240 beats/min) in eight control dogs, LV pressure did not change from 119 +/- 2 mm Hg, and mean velocity of circumferential fiber shortening (VCF) did not change from 1.25 +/- 0.09/sec. In seven dogs with LV hypertrophy, atrial pacing (240 beats/min) decreased systolic LV function; that is, LV systolic pressure decreased (p less than 0.01) by 65 +/- 12 from 254 +/- 14 mm Hg, and VCF decreased (p less than 0.01) by 0.19 +/- 0.03 from 0.97 +/- 0.15/sec. Diastolic dysfunction was also observed in the dogs with LV hypertrophy. In the control dogs during atrial pacing (240 beats/min), LV end-diastolic pressure decreased (p less than 0.01) by 8 +/- 1 from 9 +/- 1 mm Hg, end-diastolic stress decreased (p less than 0.01) by 18 +/- 2 from 22 +/- 2 g/cm2, and the radial myocardial stiffness constant did not change from 5.6 +/- 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Parasympathetic coronary vasoconstriction induced by nicotine in conscious calves.

We studied the effects of intracoronary injection of nicotine and acetylcholine on coronary blood flow in nine conscious calves chronically instrumented to measure coronary blood flow, left ventricular (LV) and mean arterial pressure, LV dP/dt, and heart rate. Nicotine (5 micrograms/kg i.c.) elicited a biphasic response in coronary blood flow consisting of an initial vasoconstriction (phase 1; blood flow fell by 52 +/- 5.4% from a baseline of 66 +/- 7.5 ml/min) followed by vasodilation (phase 2, blood flow rose 119 +/- 12.7% above baseline). The change in coronary blood flow with nicotine was not associated with changes in LV systolic pressure, mean arterial pressure, or heart rate. The change in coronary blood flow was unaffected by combined alpha- and beta-adrenoceptor blockade with prazosin, rauwolscine, and propranolol but was abolished by either muscarinic blockade with atropine or ganglionic blockade with hexamethonium. Acetylcholine (0.5 microgram/kg i.c.), without affecting mean arterial pressure, elicited changes in coronary blood flow similar to those observed with nicotine, producing an initial phase of coronary vasoconstriction (blood flow fell by 71 +/- 4.9%) followed by vasodilation (blood flow rose by 228 +/- 20.7%). Both phases of the response to acetylcholine were abolished by muscarinic blockade but were unaffected by ganglionic blockade. When nicotine was injected into the left circumflex coronary artery, no change in blood flow was observed in the left anterior descending coronary artery, indicating the lack of involvement of global reflex pathways. These results suggest that nicotine locally stimulates parasympathetic nerves, which constrict the coronary circulation via a muscarinic mechanism.

Acetylcholine↗

PubMed1988

Opiate receptor-mediated decrease in renal nerve activity during hypotensive hemorrhage in conscious rabbits.

Effects of hemorrhage on renal nerve activity and of subsequent opiate receptor blockade with naloxone were studied in conscious rabbits. Mean arterial pressure remained constant at 77 +/- 2 mm Hg through 17 +/- 2 ml/kg hemorrhage, while renal nerve activity increased by 159 +/- 16%. After 25 +/- 1 ml/kg hemorrhage, mean arterial pressure fell by 42 +/- 3 mm Hg, and renal nerve activity decreased below the prehemorrhagic control level by 41 +/- 15%. Bolus injection of naloxone (3 mg/kg i.v.) increased mean arterial pressure to 79 +/- 2 mm Hg, not significantly different from the prehemorrhagic control level. Renal nerve activity increased by 171 +/- 28%, comparable to the peak increase during nonhypotensive hemorrhage. On a different day, hemorrhage was repeated, and phenylephrine was infused during the subsequent hypotension. Phenylephrine increased mean arterial pressure to the prehemorrhagic control level. With increasing mean arterial pressure, renal nerve activity increased from its level during hypotensive hemorrhage and recovered toward the prehemorrhagic control level (-26 +/- 11%), but it did not return to the peak value reached during nonhypotensive hemorrhage. To further examine the blocking effects of naloxone on changes in mean arterial pressure and renal nerve activity induced by exogenous opiate peptides, methionine-enkephalin was injected both in the control state and after treatment with naloxone. A bolus injection of methionine-enkephalin (10 micrograms/kg) decreased mean arterial pressure (-8.1 +/- 2.0 mm Hg) and renal nerve activity (-95 +/- 1%). Pretreatment with naloxone (0.5 mg/kg) effectively blocked this depressor effect and reduction in renal nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗