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.
Tagawa
T
T
Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Imaizumi
T
T
Endo
T
T
Shiramoto
M
M
Hirooka
Y
Y
Ando
S
S
Takeshita
A
A
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