Modulation of genetic hypertension by short-term avp v1a or v2
receptor antagonism in young shr.
Naitoh, Mareo, Louise M Burrell, John Risvanis, Kathryn L Aldred,
Melinda D Rockell, Colin I Johnston, and Paddy A Phillips.
Department of Medicine, University of Melbourne, Austin &
Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
APStracts 3:0196F, 1996.
To characterize the role of vasopressin (AVP) V1A or V2 receptors and
the possible interaction with the renin-angiotensin system in the
pathogenesis of hypertension in spontaneously hypertensive rats
(SHR), young male SHR were treated from 6 to 10 weeks of age with:
AVP V1A receptor blockade; angiotensin converting enzyme (ACE)
inhibition; combination of V1A receptor blockade and ACE inhibition;
V2 receptor blockade; and vehicle. Treatments were then withdrawn,
and systolic blood pressure (SBP) was measured until 19 weeks of age.
At both 10 and 19 weeks of age, SBP was significantly reduced with
V1A receptor blockade, ACE inhibition, and combined treatment
compared to vehicle treatment, although no treatment normalized SBP
to levels of Donryu normotensive rats. Throughout the experimental
period, no significant additive effects were observed with combined
treatment. At 10 weeks of age, plasma AVP concentration and 24-hour
urinary AVP excretion were increased with AVP V2 receptor blockade.
At 19 weeks of age, SBP was significantly higher in rats previously
treated with V2 receptor blockade (233+/-3 mmHg) than with vehicle
(221+/-2 mmHg) (p< 0.01). Left ventricular mass was
significantly reduced in rats previously treated with ACE inhibition
or combined treatment. These results suggest that AVP (via V1A
receptors) and angiotensin II contribute to the pathogenesis of SHR
hypertension, whilst the AVP V2 receptor may be involved in
preventing the full expression of the hypertension, in male SHR.
Received 2 February 1996; accepted in final form 31 October 1996.
APS Manuscript Number F35-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996