AJP - Heart and Circulatory Physiology, Vol 247, Issue 6 946-H951, Copyright © 1984 by American Physiological Society
Hypertension after ending captopril administration: pathogenesis in 2-kidney, 1-clip rat
J. M. DeForrest, J. S. Creekmore and R. A. Ferrone
We have previously shown that continuous captopril administration prevents
hypertension from developing in the two-kidney, one-clip (2K, 1C) rat. The
present investigation was designed to determine the mechanism(s) producing
the hypertension. In one series of experiments captopril prevented pressure
from increasing during an 8-wk treatment period. Relative to the last day
of treatment, mean arterial pressure and total peripheral resistance (TPR)
were increased and cardiac output was unchanged at 3, 7, and 28 days after
captopril cessation. Plasma renin activity (PRA) was unchanged 3, 7, and 14
days after captopril cessation but was elevated at 28, 49, and 56 days
after captopril cessation only in 2K, 1C rats with severe hypertension
(systolic blood pressure greater than 180 mmHg). Guanethidine (45 mg/kg po,
bid) did not prevent the development of 2K, 1C hypertension but did prevent
the hypertension from developing after cessation of captopril. Blockade of
the prostaglandin system with indomethacin (5 mg/kg + 50 micrograms X kg-1
X min-1) and of the kallikrein-kinin system with aprotinin (25,000 KIU +
150 KIU X kg-1 X min-1) for 2 h had no effect on captopril's
antihypertensive effect. Additionally, no change in sodium or water balance
was observed after captopril cessation. Taken together these data
demonstrate that hypertension after captopril cessation is due to an
increase in TPR. Additionally, the rise in TPR is due to both the
sympathetic nervous and the renin-angiotensin systems since both systems
must be functional before pressure rises.
