Mukawa H, Toki Y, Shimauchi A, Okumura K, Ito T
The angiotensin type II receptor may partly be involved in
antihypertensive effects exerted by type I receptor antagonists
in hypertensive rat
12th Annual ASH Meeting
Am J Hypertens
(Apr) 10:154A 1997
The purpose of the study was to investigate the role of angiotensin enzyme
receptor types
1 (AT1) and 2 (AT2) in myocardial hypertrophy in the rat. Others had
previously alluded
to a direct effect of angiotensin on myocardial protein synthesis (J Clin
Hypertens 3:87-103,1987) and established the presence of both types of
receptors and their regulation in the hypertrophied rat myocardium (Circ
Res
73:439-447).
Five groups of 7 rats each were: 1) Sham operated; 2) Hypertensives:
aorta constricted above renal artery (Controls), 3) Hypertensive rats
injected daily with a type 1 AII receptor inhibitor (TCV-116), 4)
Hypertensive rats injected daily with a type 2 AII receptor inhibitor
(PD123319), 5) Hypertensive rats injected daily with both inhibitor types.
After 4 weeks of treatment, the measurement listed in the table below were
taken
Systolic BP increased with aortic constriction from about 106 to 188 mm Hg.
Rats treated with type
1 AII inhibitor had no rise in SBP at all (mean SBP 109), whereas blockade of
type 2 AII receptors
only had no effects on SBP (178 mm Hg). Interestingly, concomitant treatment
with both type 1 and
type 2 AII receptor inhibitors attenuated the effect of the type 1 AII
blocker on SBP (mean SBP 125
mm Hg). Similar effects were seen on LV wall thickness: an increase in
controls, no increase in
type 1 AII Rx, and attenuation of protection when type 1 and type 2 AII
blockers were given
concomitantly.
Comment: The authors conclude that
the effect of type 1 AII receptor blockers on SBP and LV mass are mediated
not only by blockade of the type 1 receptors per se, but also by indirect
activation of type 2
AII receptors (by allowing increased free AII to bind to available type 2
receptors).
(Samy S. Iskandar, MBBCh, PhD, Bowman Gray School of Medicine, Winston-
Salem, NC)
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12th Annual ASH Meeting
H: Drug therapy :
ACE inhibitors