Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels.
Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms; vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor. However, the mechanism of AVP-induced vasodilation is not known. We investigated whether AVP-induced vasodilation is mediated by nitric oxide (NO) in human forearms by examining the effects of L-arginine (a precursor of NO) and NG-monomethyl-L-arginine (L-NMMA, a blocker of NO synthase) on AVP-induced vasodilation. AVP was infused intraarterially at doses of 0.05, 0.1, 0.2, 0.5, and 1.0 ng/kg per min (n = 8). The lower doses of AVP (< or = 0.1 ng/kg per min) increased, whereas the higher doses of AVP (> or = 0.5 ng/kg per min) decreased forearm vascular resistance (FVR) (P < 0.01). Intraarterially infused L-arginine at 10 mg/min did not alter arterial pressure, baseline FVR, or heart rate. L-arginine did not alter the magnitude of AVP-induced vasoconstriction at the lower doses, but L-arginine augmented the magnitude of AVP-induced vasodilation at doses of 0.2 (P < 0.05), 0.5 (P < 0.01), and 1.0 (P < 0.05) ng/kg per min. In another group (n = 6), intraarterially infused L-NMMA (4 mumol/min for 5 min) increased baseline FVR without systemic effects, and inhibited acetylcholine-induced vasodilation (P < 0.01). L-NMMA at this dose inhibited AVP-induced vasodilation (P < 0.01) but did not affect vasoconstriction. L-arginine reversed the inhibitory effect of L-NMMA. Our results suggest that the vasodilatory effect of AVP may be mediated by NO in human forearms.
Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
T
T
Tagawa
T
T
Imaizumi
T
T
Endo
M
M
Shiramoto
Y
Y
Hirooka
S
S
Ando
A
A
Takeshita
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005542:Forearm; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D001127:Arginine Vasopressin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine