Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Mar 2004
Prazosin potentiates the acute hypotensive effects of nitroglycerin but does not attenuate nitrate tolerance in normal conscious rats.
Sympathetic activation has been suggested as a mechanism of acute nitrate tolerance, but the available literature is not definitive. We investigated the effects of prazosin, an alpha1-adrenoceptor antagonist, on acute nitroglycerin (NTG) hemodynamics and tolerance development in normal conscious rats. The effect of prazosin bolus injection (300 microg/kg) on NTG hemodynamics was first determined after acute dosing. ⋯ The hypotensive effect produced by the 30-microg NTG CD lasted for 7 +/- 2 and 10 +/- 2 seconds for prazosin-treated and untreated groups, respectively (P > 0.05, ANOVA). Our results showed that, in both NTG-tolerant and control animals, prazosin only slightly potentiated the maximum hypotensive effects of a challenge NTG dose, but did not significantly alter the pharmacodynamics of NTG-induced hemodynamic tolerance. Thus, in our animal model, sympathetic blockade by prazosin neither prevented nor attenuated in vivo tolerance induced by NTG.
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J. Cardiovasc. Pharmacol. · Sep 2003
The effect of EGb-761 on morphologic vasospasm in canine basilar artery after subarachnoid hemorrhage.
This study investigated the effects of Ginkgo biloba extract (EGb-76l), an anti-oxidant and platelet-activating factor antagonist, on basilar artery vasospasm in an experimental canine subarachnoid hemorrhage model. Morphometric analyses were performed, and serum and cerebrospinal fluid endothelin-l levels were measured by radioimmunoassay. Comparisons were made between treated and untreated groups. ⋯ Histopathological examination revealed marked vasospasm. In group 3, the serum and cerebrospinal fluid endothelin-1 levels followed the same pattern observed in group 2; however, the arteries showed significantly less vasospasm than that observed in group 2. The study findings did not provide information about the mechanism of action of the platelet-activating factor-antagonist EGb-761, but they clearly show that this agent decreases morphologic vasospasm in the dog basilar artery.
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J. Cardiovasc. Pharmacol. · May 2003
Randomized Controlled Trial Clinical TrialEffect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction.
Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). ⋯ Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.
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J. Cardiovasc. Pharmacol. · May 2003
Comparative StudyEffect of beta-adrenoceptor antagonist and angiotensin-converting enzyme inhibitor on hypertension-associated changes in adenylyl cyclase type V messenger RNA expression in spontaneously hypertensive rats.
Adenylyl cyclase (AC) messenger RNA (mRNA) expression is decreased in failing hearts. Diminished expressions are accompanied by desensitization of beta-adrenergic signal transduction. Factors contributing to such changes in mRNA expression for the major myocardial isoform AC V are not well established. ⋯ Blood pressure and left ventricular weight relative to body weight were markedly decreased by enalapril and were moderately decreased by atenolol. Expression of AC V mRNA in SHRs at 12 weeks was normalized equally by enalapril and atenolol to the level of WKYs. Thus AC V mRNA expression increases are blunted in the early stages of LVH in SHRs under the influences of beta(1)-adrenergic signal transduction and the RAS.
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J. Cardiovasc. Pharmacol. · Jan 2003
Comparative StudyEffect of the addition of a beta-blocker on left ventricular remodeling and prognosis in patients with dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitor.
To examine the effect of the addition of a beta-blocker in the treatment of chronic heart failure due to dilated cardiomyopathy, we compared the change of left ventricular remodeling and the prognosis between patients treated with angiotensin-converting enzyme inhibitors and patients who had beta-blockers added to angiotensin-converting enzyme inhibitors. Fifty-seven patients were treated with an angiotensin-converting enzyme inhibitor in addition to combination therapy with furosemide, spironolactone and digoxin. In 60 patients, a beta-blocker was administered in addition to combination therapy with furosemide, spironolactone, digoxin and an angiotensin-converting enzyme inhibitor. ⋯ The event-free rate and the cumulative survival rate during the follow-up periods were markedly better in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group (p = 0.0019 and p = 0.0099, respectively). These results indicate that the suppression of left ventricular remodeling and the improvement of prognosis in patients with dilated cardiomyopathy are markedly stronger in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group. Thus, beta-blocker should be added to patients with dilated cardiomyopathy treated with an angiotensin-converting enzyme inhibitor.