Attenuation of genetic hypertension after short-term vasopressin V1A receptor antagonism.
Abnormalities of the vasopressin system are found in genetic hypertension. This study compares the delayed effects of a brief period of vasopressin V1A receptor blockade and angiotensin-converting enzyme inhibition in young female and male spontaneously hypertensive rats (SHR) on the development of hypertension in adult life. In a separate study, the role of vasopressin in the maintenance of blood pressure in adult SHR was assessed. Young SHR received either the nonpeptide vasopressin V1A receptor antagonist OPC-21268, the angiotensin-converting enzyme inhibitor ramipril, or vehicle from 6 to 10 weeks of age. During the treatment period, OPC-21268 and ramipril reduced systolic blood pressure compared with control SHR (P < .001). Blood pressure in male SHR 7 weeks after treatment withdrawal was 178 +/- 1 mm Hg in ramipril-treated, 184 +/- 1 mm Hg in OPC-21268-treated, and 200 +/- 2 mm Hg in control SHR (P < .001). Similar results were seen in female SHR, although both OPC-21268 and ramipril were less effective antihypertensive agents in female compared with male SHR. The sustained attenuation in blood pressure was not associated with significant cardiovascular structural changes (left ventricular-to-body weight ratio, renal weight-to-body weight ratio, mesenteric resistance artery media-to-lumen ratio). Results of vasopressin V1A receptor binding kinetics and plasma renin or aldosterone concentrations did not suggest a lasting effect of OPC-21268 on the vasopressin system or of ramipril on the renin-angiotensin system following treatment withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Burrell
L M
LM
University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Phillips
P A
PA
Risvanis
J
J
Aldred
K L
KL
Hutchins
A M
AM
Johnston
C I
CI
D000375:Aging; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure; D001835:Body Weight; D005260:Female; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; C068644:OPC 21268; D017257:Ramipril