RESPONSES TO VASOPRESSIN AND DESMOPRESSIN OF HUMAN CEREBRAL-ARTERIES

The effects of vasopressin and deamino-8-D-arginine vasopressin (desmo pressin) were studied in isolated rings from branches (0.8-1.2 mm in e xternal diameter) of human middle cerebral arteries obtained during au topsy of 27 patients who had died 3 to 10 hr before. In arterial rings under resting tension, vasopressin produced concentration-dependent c ontractions with an EC(50) of 7.2 x 10(-10) M. The vasopressin V-1 rec eptor antagonist ta-mercapto-beta,beta-cyclopentamethylenepropionic ci d)-2-(O-methyl)-tyrosine-8-arginine)vasopressin] (10(-6) M) displaced the control curve to vasopressin 1250-fold to the right in a parallel manner. The mixed V-1-V-2 receptor antagonist ta-mercapto-beta,beta-cy clopentamethylenepropionic sine-4-valine-8-arginine-9-desglycine)vasop ressin] (10(-8) M) depressed both the slope and maximal response of th e control curve for vasopressin. Vasopressin produced further contract ions in arterial rings with or without endothelium precontracted with prostaglandin F-2 alpha or norepinephrine. In precontracted arterial r ings and previously treated with the V-1 vasopressinergic antagonist t a-mercapto-beta,beta-cyclopentamethylenepropionic cid)-2-(O-methyl)-ty rosine-8-arginine)vasopressin] (10(-6) M) vasopressin caused endotheli um-indpendent relaxation. The relaxation to vasopressin was reduced si gnificantly by indomethacin (10(-6) M) and unaffected by the V-1-V-2 r eceptor antagonist [(1-(beta-mercapto-beta, beta-cyclopentamethylenepr opionic sine-4-valine-8-arginine-9-desglycine)vasopressin] (10(-6) M) or by N-G-monomethyl-L-arginine (10(-4) M). The selective V-2 receptor agonist deamino-8-D-arginine vasopressin caused concentration-depende nt relaxations in precontracted arterial rings that were inhibited by the mixed V-1-V-2 receptor antagonist but not by the V-1 receptor anta gonist or by pretreatment with N-G-monomethyl-L-arginine. These observ ations indicate that vasopressin is primarily a constrictor of human c erebral arteries by V-1 receptor stimulation. Vasopressin causes dilat ation of human cerebral arteries only if V-1 receptor blockade is pres ent. This relaxation appears to be mediated by the release of vasodila tor prostaglandins and is independent of V-2 receptor stimulation or r elease of nitric oxide. In contrast, deamino-8-D-arginine vasopressin elicits relaxation that is largely dependent on V-2 receptor stimulati on.