Effect of chlorethylclonidine on arterial blood pressure and heart rate in the conscious rat

M. T. Piascik, M. S. Sparks, T. A. Pruitt

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The effect of chlorethylclonidine (CEC) on arterial blood pressure and heart rate (HR) has been evaluated in the conscious rat. CEC injection (25 mg/kg i.p.) caused a statistically significant decrease in mean arterial blood pressure (MAP) that was seen 24 hr after treatment. CEC also induced a decrease in HR that was maximal at 45 min but returned to pretreatment levels after 3 hr. CEC had no effect on the ability of isoproterenol to increase HR. CEC treatment had little effect on the pressor dose-response curve of either phenylephrine or BHT 920. When injected into the brain (25 mg/kg, lateral ventricle), CEC had no effect on MAP or HR. Yohimbine injected into the lateral ventricle had no effect on the response to i.p. CEC. Prazosin, used as a standard for comparison, caused a larger fall in MAP than CEC and this hypotension was associated with tachycardia and a marked shift (>300-fold) in the phenylephrine pressor dose-response curve. A reactive analog of prazosin, SZL-49 {1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo[2,2,2]octa- 2,5-diene-2-carbonyl)piperazine}, had effects similar to prazosin on MAP and HR. These data show that: 1) CEC and prazosin have a different spectrum of effects; 2) CEC produced a decrease in MAP and HR and had little effect on phenylephrine or BHT 920 responsiveness; 3) the fall in MAP induced by prazosin and SZL-49 was associated with a significant tachycardia and impairment of phenylephrine pressor activity; 4) the hypotensive and bradycardic actions of CEC are not due to blockade of peripheral alpha-2 or beta-1 adrenoceptors or to a stimulation of central alpha-2 adrenoceptors. These data suggest that the alpha-1(b) antagonist CEC and prazosin may induce hypotension by different mechanisms.

Original languageEnglish
Pages (from-to)901-906
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume262
Issue number3
StatePublished - 1992

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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