Modulation of genetic hypertension by short-term AVP V1A or V2 receptor antagonism in young SHR.
To characterize the role of arginine vasopressin (AVP) V(1A) 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 wk of age with AVP V(1A) receptor blockade, angiotensin-converting enzyme (ACE) inhibition, combination of V(1A) receptor blockade and ACE inhibition, V2 receptor blockade, and vehicle. Treatments were then withdrawn, and systolic blood pressure (SBP) was measured until 19 wk of age. At both 10 and 19 wk of age, SBP was significantly reduced with V(1A) receptor blockade, ACE inhibition, and combined treatment compared with 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 wk of age, plasma AVP concentration and 24-h urinary AVP excretion were increased with AVP V2 receptor blockade. At 19 wk 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 V(1A) receptors) and angiotensin II contribute to the pathogenesis of SHR hypertension, whereas the AVP V2 receptor may be involved in preventing the full expression of the hypertension, in male SHR.
Naitoh
M
M
Department of Medicine, University of Melbourne, Austin, Australia.
Burrell
L M
LM
Risvanis
J
J
Aldred
K L
KL
Rockell
M D
MD
Johnston
C I
CI
Phillips
P A
PA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood / Q000652:urine; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000235:genetics*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism / Q000502:physiology*; D011919:Rats, Inbred Strains; D013599:Systole; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D010880:Piperidines; D015363:Quinolones; D001127:Arginine Vasopressin; C068644:OPC 21268; C076251:mozavaptan; D017257:Ramipril