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

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.