Cardiovascular and renin responses to desmopressin in humans: role of prostacyclin and beta-adrenergic systems.
To investigate the involvement of prostacyclin and the sympathetic nervous system in cardiovascular responses to 1-desamino-8-D-arginine vasopressin (DDAVP), a selective V2-receptor agonist, in normal subjects, DDAVP (0.4 micrograms/kg) was infused with or without indomethacin, a cyclooxygenase inhibitor, or propranolol, a beta-adrenoceptor antagonist. A decrease in blood pressure and increases in pulse rate and plasma renin activity (PRA) were observed by DDAVP infusion. Indomethacin did not influence the DDAVP-induced changes in blood pressure and pulse rate but suppressed the increases in PRA and urinary 6-ketoprostaglandin F1 alpha excretion after DDAVP infusion. Even with propranolol administration, DDAVP produced a similar decrease in blood pressure with a reduction of the increased pulse rate. The DDAVP-induced increase in PRA was not affected either. Indomethacin or propranolol alone did not affect the basal levels of the parameters. DDAVP stimulated the in vitro renin release from rabbit renal cortical slices. The stimulation was inhibited by indomethacin or d(CH2)5[D-Ile2,Ile4]AVP, a selective V2-receptor antagonist. These findings suggest that DDAVP primarily elicits vasodilation, probably through the prostacyclin-independent endothelium-derived relaxation and DDAVP also causes an increase in renin release, which would be partly attributed to the increased synthesis of prostacyclin due to vasculoendothelial V2-like receptor activation but not mainly due to an increase in sympathetic nerve activity.
Hasunuma
K
K
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Yamada
K
K
Tamura
Y
Y
Yoshida
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011674:Pulse / Q000187:drug effects; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012083:Renin / Q000097:blood* / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D015121:6-Ketoprostaglandin F1 alpha; D011433:Propranolol; D011464:Epoprostenol; D012083:Renin; D003894:Deamino Arginine Vasopressin; D007213:Indomethacin