Acute tolerance to clonidine hypotension and bradycardia in normotensive and hypertensive rats.
Tolerance to the antihypertensive effect of clonidine has been observed in humans but there are few studies showing either acute or chronic tolerance to clonidine hypotension in experimental animals. We determined whether tachyphylaxis to acute clonidine hypotension could be demonstrated in normotensive Sprague Dawley rats by i.v. injections of 2 repetitive clonidine doses of either 1.5, 3.0, 5.0, or 10.0 micrograms/kg, or in SHR rats by repeated intracerebroventricular injections of 1.5 or 3.0 micrograms/kg, while monitoring arterial blood pressure. Second doses of clonidine were given 30 minutes after recovery of arterial pressure from the first dose. At 3.0 micrograms/kg and greater, the hypotension produced by the second dose was at least 50% less than that elicited by the first dose. By contrast, no acute tachyphylaxis was observed to the decrease in tension caused by clonidine in the transmurally stimulated isolated guinea pig ileum after 2 repeated exposures to clonidine, with intervening wash, at concentrations between 5 X 10(-10) M to 5 X 10(-8) M. Also, no tachyphylaxis occurred to the initial hypertensive phase of clonidine in Sprague Dawley rats.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004361:Drug Tolerance; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013618:Tachyphylaxis
D003000:Clonidine