Prolonged stimulation of intrarenal V1 vasopressin receptors results in sustained hypertension.
In an earlier study, we reported that chronic intravenous administration of the V1 agonist [Phe2,Ile3,Orn8]vasopressin (V1AG) results in sustained hypertension. The present study was designed to determine whether V1-induced hypertension may be related specifically to intrarenal actions of this peptide. Chronic infusion of the V1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng.kg-1.min-1 for 14 days resulted in a sustained rise of 18 mmHg of mean arterial pressure (MAP). After withdrawal of V1AG, MAP returned to the baseline level. During the first day of V1AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V1AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V1 antagonist d(CH2)5[Tyr(Me)2,Ala-NH(2)9]AVP in equimolar amounts (2.5 ng.kg-1.min-1) prevented the MAP increase elicited by intravenous V1AG. However, intravenous administration of the V1 antagonist at the same rate together with V1AG (n = 7) failed to prevent hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V1 vasopressin receptors. They also suggest that some V2 agonistic properties of AVP may restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.
Medical Academy of Warsaw, Poland.
E
E
Szczepanska-Sadowska
K
K
Stepniakowski
M M
MM
Skelton
A W
AW
Cowley
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007679:Kidney Medulla / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008297:Male; D009951:Ornipressin / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000819:agonists / Q000502:physiology*; D013997:Time Factors; D014667:Vasopressins / Q000008:administration & dosage / Q000494:pharmacology*
D017483:Receptors, Vasopressin; C082351:vasopressin, Phe(2)-Ile(3)-Orn(8)-; D014667:Vasopressins; D001127:Arginine Vasopressin; D009951:Ornipressin