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-N(G)-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. This evidence suggests that DDAVP evokes the endothelium-dependent in vitro vasorelaxation that is caused by DDAVP-induced NO production in the endothelium. This action is not via the authentic V2 receptor but rather via the endothelial V1-like receptors, which are functionally different from the V1 receptor in smooth muscle cells.
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|Issue number||2 27-2|
|Publication status||Published - 1993|
- nitric oxide production
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology (medical)