V2-receptor-mediated relaxation of human renal arteries in response to desmopressin.
The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (10(-4) mol/L). Two V1 receptor antagonists (a peptidic and a nonpeptidic) had no effect on desmopressin-induced relaxation. However, V2 receptor antagonists (three peptidic and a nonpeptidic) reduced significantly (P < .05) the maximal response to desmopressin. The results of this study show that desmopressin exerts powerful endothelium-dependent relaxation of human renal arteries, probably through stimulation of V2-like receptors that may bring about the release of dilating prostaglandins.
Medina
P
P
Departamento de Fisiología, Universidad de Valencia, Spain.
Segarra
G
G
Vila
J M
JM
Chuan
P
P
Domenech
C
C
Lluch
S
S
D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000502:physiology*; D012076:Renal Agents / Q000494:pharmacology*; D012077:Renal Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D065092:Antidiuretic Hormone Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D017483:Receptors, Vasopressin; D012076:Renal Agents; D019001:Nitric Oxide Synthase; D003894:Deamino Arginine Vasopressin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin