Endothelium-dependent vasorelaxation evoked by desmopressin and involvement of nitric oxide in rat aorta.
It is known that in vivo administration of desmopressin (DDAVP; a selective V2-vasopressin receptor agonist) results in prostacyclin-independent vasodilation. The in vitro effects of DDAVP and its mechanisms were examined using rat aortic strips. DDAVP from a concentration of 1 x 10(-9) M caused a concentration-dependent relaxation of the aorta precontracted with norepinephrine (10(-7) M) with intact endothelium. However, no relaxation was induced in aorta with the endothelium removed. The DDAVP-induced relaxation was not influenced by the presence of indomethacin but was inhibited by L-NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide (NO) synthesis. The inhibition by L-NMMA was reversed by the addition of L-arginine but not D-arginine. Further, the endothelium-dependent relaxation due to DDAVP was potentiated by superoxide dismutase, a scavenger of superoxide anions, and was inhibited by hemoglobin. DDAVP induced an increase in guanosine 3',5'-cyclic monophosphate levels in the aorta with endothelium but not in aorta without endothelium, and this was suppressed by L-NMMA and hemoglobin. The suppression by L-NMMA was also partially reversed by L-arginine but not by D-arginine. Two selective V2-receptor antagonists had no effect on the DDAVP-induced vasorelaxation. Selective V1-receptor antagonists (a peptidic and a nonpeptidic) caused a concentration-dependent but nonparallel shift to the right of the concentration-response curves to DDAVP. However, DDAVP did not affect the tension of the strip with or without endothelium in nonprecontracted aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Clinical Research and Internal Medicine, Sakura National Hospital, Chiba, Japan.
K
K
Yamada
M
M
Nakayama
H
H
Nakano
N
N
Mimura
S
S
Yoshida
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation; D019323:omega-N-Methylarginine
D065092:Antidiuretic Hormone Receptor Antagonists; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase; D003894:Deamino Arginine Vasopressin; D006152:Cyclic GMP