Attenuation of spontaneous hypertension in rats by a vasopressin antagonist.
Although abnormalities in the vasopressin system have been reported in spontaneously hypertensive rats (SHR), neither short-term nor long-term administration of the vasopressin antagonist d(CH2)5-Tyr(Me)arginine vasopressin (AVP), which selectively blocks the action of vasopressin on vascular (V1) receptors, altered the course of hypertension in SHR. In the current study, long-term administration of a different vasopressin antagonist, d(CH2)5-D-Tyr(Me)VAVP, to SHR and Wistar-Kyoto rats (WKY) from 4 to 12 weeks of age significantly attenuated the development of systolic hypertension in SHR (p less than 0.05) without altering blood pressure in normotensive WKY. The antagonist was delivered subcutaneously by osmopump at 0.1 microgram/hr. Systolic blood pressure was monitored twice weekly by tail plethysmography beginning at 5 weeks of age. In a second group of SHR, the drug infusion was continued until 18 weeks of age. In this group, the attenuation of systolic hypertension by the drug was extended and became more prominent (p less than 0.007). Resting mean arterial pressure measured by indwelling catheters in the conscious state at 18 weeks of age was significantly reduced in the antagonist-treated SHR (144 +/- 4 vs 157 +/- 4 mm Hg; p less than 0.05). Heart rate also was significantly reduced by the drug (351 +/- 6 vs 392 +/- 7 beats/min; p less than 0.001). Following measurement of mean arterial pressure in the rats at 18 weeks of age, the osmopumps were removed and systolic blood pressure, mean arterial pressure, and heart rate were observed until 22 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Sladek
C D
CD
Department of Neurology, University of Rochester School of Medicine, New York.
Blair
M L
ML
Sterling
C
C
Mangiapane
M L
ML
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000032:analysis; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D012083:Renin / Q000032:analysis; D014667:Vasopressins / Q000037:antagonists & inhibitors*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D014667:Vasopressins; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; C028883:argipressin, beta-mercapto beta,beta-cyclopentamethylenepropionic acid(1)-O-methyl-Tyr(2)-Val(4)-; D012083:Renin