Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Dec 1997
Randomized Controlled Trial Clinical TrialEffects of beta-adrenoceptor agonists and antagonists on heart-rate variability in normal subjects assessed using summary statistics and nonlinear procedures.
The influence of celiprolol (beta1- and beta2-adrenoceptor partial agonist), propranolol (beta1- and beta2-adrenoceptor antagonist), and atenolol (beta1-adrenoceptor antagonist) on heart-rate variability (HRV) was assessed from Holter records in 12 normal volunteers. A combination of summary statistics and nonlinear procedures was used to assess HRV and autonomic balance. Under double-blind and randomised conditions (Latin-square design), subjects received placebo, celiprolol (200 and 800 mg), propranolol (160 mg), atenolol (50 mg), and combinations of these agents. ⋯ Celiprolol increased the frequency of consecutive cardiac accelerations; the duration between and variance of these beat-to-beat differences shortened after celiprolol but lengthened with increased variance after propranolol and atenolol. These results demonstrated reduced HRV indices and a shift toward sympathetic dominance after the beta-adrenoceptor agonist celiprolol contrasting with increased HRV indices and parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and atenolol. The implications of these findings for the treatment of patients with cardiovascular disease warrant further study.
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J. Cardiovasc. Pharmacol. · Nov 1997
Cardiovascular effects of central choline during endotoxin shock in the rat.
The cardiovascular effects of intracerebroventricular (i.c.v.) administration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachycardia within 10 min of treatment. Choline (50, 100, and 150 microg; i.c.v.) increased blood pressure and decreased heart rate in this condition in a dose-dependent manner. ⋯ The vasopressin receptor antagonist, (beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1)-O-Me-Tyr2,Arg8 )-vasopressin (10 microg/kg; i.v.) administered 5 min after choline decreased blood pressure from the increased level to the precholine levels but did not alter bradycardia. These results indicate that, in rats treated with endotoxin, choline increases blood pressure and decreases heart rate by a presynaptic mechanism leading to the activation of central nicotinic cholinergic pathways. An increase in plasma vasopressin levels seems to be involved in the pressor, but not in the bradycardic response, to choline.
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J. Cardiovasc. Pharmacol. · Oct 1997
Effects of bradykinin and icatibant on renal hemodynamics in conscious spontaneously hypertensive and normotensive rats.
We investigated the effects of bradykinin (BK) and icatibant (HOE 140), a highly selective bradykinin-B2-receptor antagonist, on mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), and renal vascular resistance (RVR) in conscious Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Experiments were performed in conscious male WKY rats and SHRs instrumented over the long term with arterial and venous catheters and a transit-time flow probe for measurement of RBF. In WKY rats (n = 16), intraaortic (i.a.) bolus injections of BK (0.1, 1.0, and 10 microg) produced dose-dependent decreases in MAP and RBF with reciprocal increases in RVR. ⋯ Our results provide evidence that BK exhibits renal vasoconstrictor and vasodilator properties in vivo, both mediated by B2-receptors. Furthermore, we demonstrated that SHRs display an increased B2-receptor-mediated vasodilatory responsiveness to BK. Finally we showed that blockade of B2 receptors leads to an increase of MAP in SHRs in contrast to WKY rats, suggesting an important role of the kallikrein/kinin system in the regulation of high blood pressure in SHRs.
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J. Cardiovasc. Pharmacol. · Jun 1997
Effects of a new cardiotonic phosphodiesterase III inhibitor, olprinone, on cardiohemodynamics and plasma hormones in conscious pigs with heart failure.
We examined the effects of a novel phosphodiesterase III inhibitor, olprinone, on the cardiohemodynamics and plasma hormones in conscious pigs with pacing-induced heart failure. After pacing for 5-10 days, cardiac output (CO) decreased from 2.25 +/- 0.17 to 1.67 +/- 0.13 L/min (n = 8, p < 0.01) and stroke volume (SV) decreased from 20.1 +/- 2.1 to 12.0 +/- 1.6 ml (n = 8, p < 0.01), whereas left arterial pressure (LAP) increased from 2.8 +/- 1.2 to 16.7 -/+ 0.9 mm Hg (n = 7, p < 0.001) and systemic vascular resistance (SVR) increased from 38.7 +/- 3.5 to 49.8 +/- 4.2 mm Hg/L/min (n = 8, p < 0.01). Sequential intravenous infusions of 0.03, 0.3, and 3.0 microg/kg/min of olprinone at 30-min intervals to eight pigs caused dose-dependent increases in the decreased CO, SV, and maximal rate of rise in left ventricular pressure (LV dP/dt(max)) and decreased the elevated LAP and SVR. ⋯ Olprinone did not affect the rate-pressure product. In addition, olprinone produced significant decreases in the plasma levels of atrial natriuretic peptide and cyclic guanosine monophosphate, with no changes in the plasma levels of cyclic adenosine monophosphate and catecholamines or plasma renin activity. These findings indicate that the short-term intravenous infusions of olprinone ameliorated the decreased left ventricular function without affecting myocardial oxygen consumption or the sympathetic nervous system in conscious pigs with heart failure.
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J. Cardiovasc. Pharmacol. · May 1997
Levosimendan enhances left ventricular systolic and diastolic function in conscious dogs with pacing-induced cardiomyopathy.
We examined the left ventricular (LV) mechanical actions of levosimendan (LSM) before and after the development of pacing-induced cardiomyopathy in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), the maximal rate of segment-lengthening velocity (dL/dt), and a regional chamber-stiffness constant (Kp). ⋯ LSM significantly (p < 0.05) increased Mw (54 +/- 3 to 98 +/- 6 mm Hg) +dP/dt and dL/dt (57 +/- 13 to 72 +/- 13 mm/s) and decreased tau (66 +/- 4 to 52 +/- 3 ms) and Kp (1.14 +/- 0.14 to 0.71 +/- 0.03 mm-1) in the presence of LV dysfunction. In contrast to the findings in normal dogs, however, LSM did not alter heart rate and calculated indices of myocardial oxygen consumption in dogs after pacing. The findings indicate that LSM produces favorable alterations in hemodynamics and positive inotropic and lusitropic effects in conscious dogs with left ventricular dysfunction.