Increased contraction to noradrenaline by vasopressin in human renal arteries

Arginine vasopressin (AVP) not only acts directly on blood vessels through vasopressin V1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments. The aim of the present study was to assess whether subpressor concentrations of AVP could contribute to an abnormal adrenergic contractile response of human renal arteries.

Renal artery rings were obtained from 27 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension.

AVP (10(-10) mol/l) and the vasopressin V1 receptor agonist [Phe2, Orn8]-vasotocin (10(-10) mol/l) produced a leftward shift of the concentration-response curve to noradrenaline (half-maximal effective concentration decreased from 1.1 x 10(-6) mol/l to 3.1 x 10(-7) mol/l). The enhancement of noradrenaline-induced contractions was inhibited by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP (10-8 mol/l) and unaffected by endothelium removal or pretreatment with the inhibitor of nitric oxide (NO) synthase NG-monomethyl-l-arginine (l-NMMA). The vasopressin V2 receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) (10(-10)-10(-8) mol/l) did not modify contractile responses to noradrenaline. In the presence of the dihydropyridine calcium antagonist nifedipine (10(-6) mol/l), vasopressin failed to enhance the contractile response to noradrenaline.

The results demonstrate that subpressor concentrations of vasopressin potentiate the contractile effects of noradrenaline without intervention of the NO system. The effects appear to be mediated by vasopressin V1 receptor stimulation, which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.