Role of endothelin and vasopressin in DOCA‐salt hypertension

The relative roles of endothelin (ET) and vasopressin (AVP) in the regulation of blood pressure (BP), cardiac output (CO) and total peripheral resistance (TPR) were investigated in the early stages (24 – 31 days) of development of hypertension in the conscious deoxycorticosterone acetate (DOCA)‐salt hypertensive rat model. BP was recorded with radiotelemetry devices and CO with ultrasonic transit‐time probes. TPR was calculated from the BP and CO recordings. The contributions of endogenous ET and AVP were studied by infusing [d(CH2)51,O‐Me_Tyr2,Arg8]‐vasopressin, a V1‐receptor antagonist, and bosentan, a mixed ETA/ETB receptor antagonist (Study 1). Vascular responsiveness was estimated from the changes in TPR evoked by i.v. infusions of ET‐1 and AVP (Study 2). In study 1, infusion of bosentan reduced TPR and BP dramatically in DOCA‐salt hypertensive rats but not in SHAM control rats, and this effect was greater when the AVP system had been blocked. In contrast, the V1 receptor antagonist alone failed to change TPR and BP in DOCA‐salt hypertensive rats. However, subsequent infusion of the V1 receptor antagonist during the plateau phase of the response in bosentan pretreated DOCA‐salt hypertensive rats led to significant decreases in both BP and TPR. In study 2, TPR and BP responses to ET‐1, but not AVP, were greater in DOCA‐salt rats than in control rats. CO responses to ET‐1 or AVP were similar in the two groups. The results suggest that both ET and AVP play a role in the maintenance of TPR and BP; when one system is blocked the other compensates. However, the magnitude of the contribution to the hypertensive state appears greater for ET than for AVP. Enhanced vascular responses to ET appear to contribute to this greater role. British Journal of Pharmacology (2001) 132, 1447–1454; doi:10.1038/sj.bjp.0703958