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-dime-thoxy-2-quinazolinyl)-4-(2- bicyclo[2,2,2]octa-2,5-diene-2-car-bonyl)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-1b antagonist CEC and prazosin may induce hypotension by different mechanisms.