Withdrawal-induced antihypertensive effect of vasopressin: role of the L-arginine/nitric oxide pathway.
The role of the endothelium-derived relaxing factor (EDRF), nitric oxide (NO), in the withdrawal-induced antihypertensive phenomenon (WAP) of arginine vasopressin (AVP) was studied in conscious unrestrained rats implanted with femoral arterial catheters for the measurement of arterial blood pressure. Cessation of a 3-h intravenous infusion of AVP (20 ng.kg-1.min-1) was followed by a large and long-lasting fall in mean arterial blood pressure below preinfusion control values in spontaneously hypertensive rats (SHR; -47.5 +/- 6.4 mmHg; 1 mmHg = 133.3 Pa) but not in normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) control rats. Chronic treatment of normotensive SD rats with the NO synthesis inhibitor, N omega-nitro-L-arginine (L-NNA; 0.5 g.L-1 in drinking water for 2 weeks), resulted in sustained hypertension. Similar to the SHR model, a large fall in blood pressure (-37.8 +/- 7.7 mmHg) was observed in this model of hypertension following cessation of the AVP infusion. In SHR, inhibition of NO synthesis with L-NNA (0.05 g.L-1 in drinking water for 2 weeks) failed to attenuate the fall in blood pressure following withdrawal of AVP. Chronic treatment with the NO precursor, L-arginine (L-Arg; 1.25 g.L-1 in drinking water for 2 weeks), did not affect the amplitude or the time course of the WAP in SHR. The results indicate that the L-Arg/NO pathway is not essential to the expression of the WAP to AVP in the SHR.
Talom
R T
RT
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
McNeill
J R
JR
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology / Q000502:physiology*; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine