Clonidine reverses the slowly developing hypertension produced by low doses of angiotensin II.
We used the centrally acting sympatholytic drug clonidine to evaluate neurogenic pressor activity in rats made hypertensive by chronic intravenous infusion of a low dose (4.0 ng.min-1) of angiotensin II (Ang II). Male Sprague-Dawley rats were instrumented with arterial and venous catheters and then housed in metabolic cages for the duration of the experiment. After 3 days of recovery from surgery, daily measurements were begun of mean arterial pressure, heart rate, water balance, and urinary electrolyte excretion. After 3 days of control measurements rats received either Ang II (4.0 ng.min-1 IV, n = 5) or saline vehicle (n = 4) continuously over a 15-day period. After the Ang II and vehicle infusions were ended, measurements were made during 3 days of recovery. On days 2, 7, and 12 of the experimental infusion period, clonidine hydrochloride was administered as a bolus (10.0 micrograms.kg-1 IA). The resulting changes in mean arterial pressure and heart rate were assessed over a 6-hour period. Fluid measurements were evaluated on a daily basis. In rats receiving only vehicle, clonidine produced no significant changes in any variable at any time. In rats given Ang II, mean arterial pressure increased from a control value (mean +/- SEM) of 106 +/- 1 mm Hg to 135 +/- 6, 139 +/- 6, and 148 +/- 4 mm Hg on days 2, 7, and 12, respectively. The antihypertensive response to clonidine after 6 hours on days 2, 7, and 12 of the Ang II infusion in these rats was -18 +/- 8, -16 +/- 5, and -23 +/- 9 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Gorbea-Oppliger
V J
VJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48823.
Fink
G D
GD
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D003000:Clonidine