Cardiovascular and renal effects of endothelin receptor blockade with PD 145065 and interaction with urodilatin

Role of endogenous endothelins (ET) in the control of cardiovascular system and renal function, and ET interaction with urodilatin (URO) were studied in anaesthetized rats. Activity of ET was blocked using PD 145065 (5 mg kg(-1) body wt i.v.), a non-selective antagonist of ET(A) and ET(B) receptors. PD 145065 decreased mean arterial blooo pressure (MBP) from 114+/-4 to 109+/-4 mmHg and the renal blood flow (RE Fl from 6.6+/-0.3 to 5.8+/-0.4 mi min(-1) (P < 0.02) and increased renal vascular resistance (RVR) from 17.7+/-1.2 to 20.1+/-2.1 mmHg min mL(-1). Heart rate (HR) and renal function were not affected. URO was infused i.v. at 0.1 nmol min(-1) kg(-1) body wt without or with previous ET receptor blockade. After pre-treatment with PD 145065. infusion oi URO decreased MBP more than did URO alone: 15+/-3% vs. 7+/-2% (P < 0.05). RVR and HR did not change after URO alone but decreased with URO given to PD 145065 treated rats (19+/-5% and 14+/-3%, respectively. P < 0.01). It is concluded that in anaesthetized surgically prepared rats endogenous ET can cause renal vasodilation, in contrast to constriction of systemic vasculature. Enhancement by ET blockade of vascular systemic and renal effects oi URO supports ET interaction with natriuretic peptides in the control of cardiovascular and renal function.