EFFECTS OF SELECTIVE ET(B)-RECEPTOR STIMULATION ON ARTERIAL, VENOUS AND CAPILLARY FUNCTIONS IN CAT SKELETAL-MUSCLE

1 This paper describes, in quantitative terms, the in vivo effects of two selective ET(B)-receptor agonists (IRL 1620 and BQ 3020) on vascular resistance (tone) in the following consecutive sections of the vascular bed of sympathectomized cat skeletal muscle: large-bore arterial resistance vessels (>25 mu m), small arterioles (<25 mu m) and the veins. The effects on capillary pressure and transcapillary fluid exchange were also recorded. 2 Both IRL 1620 and BQ 3020, infused i.a. to the muscle preparation, evoked an initial transient dilator response followed by a moderate dose-dependent constrictor response, both being preferentially confined to the small arterioles. The dilator response was associated with a transient increase, and the constrictor response with a sustained decrease, in capillary pressure, the latter causing net transcapillary fluid absorption. The capillary filtration coefficient decreased during the constrictor response, indicating constriction of terminal arterioles/precapillary sphincters. 3 The vascular responses to the ET(B)-receptor agonists were unaffected by blockade of endothelium-derived nitric oxide (N-G-nitro-L-arginine methyl ester) and by selective ET(A)-receptor blockade (FR139317). However, blockade of prostacyclin production with indomethacin decreased the amplitude of the dilator response, and decreased the time required to reach a steady-state vasoconstrictor response to the ET(B)-receptor agonists. 4 The effect of ET(B)-receptor stimulation on vascular tone was also evaluated in vitro on the cat femoral artery and vein. IRL 1620 had no effect on the femoral artery but caused a weak dose-dependent relaxation in the femoral vein. This large vein relaxation response seemed to be mediated by endothelium-derived nitric oxide and not by prostacyclin. 5 It may be concluded that ET(B)-receptor stimulation is responsible for the dilator response, and can contribute to the constrictor response, elicited by endothelins in cat skeletal muscle in vivo.