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Single and repeated doses of the vasodilator/beta-adrenergic antagonist, carvedilol, block cirazoline- and isoproterenol-mediated hemodynamic responses in the conscious rat.

Abstract
The purpose of this study was to evaluate the effects of carvedilol, a beta 1&2-adrenergic blocker and vasodilator, on cirazoline-mediated changes in arterial blood pressure and isoproterenol-mediated changes in heart rate after acute and chronic administration. Conscious, chronically instrumented male Sprague-Dawley rats were injected with carvedilol (1 mg/kg, IV), prazosin (0.3 mg/kg, IV), or propranolol (1 mg/kg, twice daily for 8 days. After administration of the first dose of carvedilol on day 1, the vasopressor response to cirazoline (60 +/- 3 mmHg predrug) and the isoproterenol-induced tachycardia (152 +/- 13 beats/min predrug) were blocked (e.g., 7 +/- 4 mmHg postdrug and 11 +/- 3 beats/min postdrug, respectively). After the administration of carvedilol on day 8, the cirazoline vasopressor response was 2 +/- 1 mmHg and the isoproterenol-induced tachycardia was 4 +/- 3 beats/min, indicating effective alpha 1- and beta-adrenergic blockade after chronic dosing with carvedilol. Prazosin blocked the cirazoline-induced vasopressor response on both days 1 and 8 but had no effect on the isoproterenol-induced tachycardia. Propranolol blocked the isoproterenol-induced tachycardia on both days 1 and 8 but had no effect on the cirazoline vasopressor response. These data indicate that only carvedilol effectively blocked both alpha- and beta-adrenergic hemodynamic responses and that the antagonism of these responses with carvedilol was not diminished after chronic dosing of twice-a-day treatment for 8 days.
AuthorsE F Smith 3rd, M J Slivjak, R Gagnon
JournalCardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 6 Issue 5 Pg. 499-504 (Oct 1992) ISSN: 0920-3206 [Print] United States
PMID1360255 (Publication Type: Journal Article)
Chemical References
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Carbazoles
  • Imidazoles
  • Propanolamines
  • Vasodilator Agents
  • Carvedilol
  • Propranolol
  • Isoproterenol
  • cirazoline
  • Prazosin
Topics
  • Adrenergic alpha-Agonists (antagonists & inhibitors)
  • Adrenergic alpha-Antagonists (pharmacology)
  • Adrenergic beta-Antagonists (pharmacology)
  • Analysis of Variance
  • Animals
  • Carbazoles (pharmacology)
  • Carvedilol
  • Hemodynamics (drug effects)
  • Imidazoles (antagonists & inhibitors)
  • Isoproterenol (antagonists & inhibitors)
  • Male
  • Prazosin (pharmacology)
  • Propanolamines (pharmacology)
  • Propranolol (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vasodilator Agents (pharmacology)

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