Endothelin-1 in the rabbit: interactions with cyclo-oxygenase and NO-synthase products

1. Endothelin-1 infusion (5-40 pmol kg-1 min-1) in the normal anaesthetized rabbit, produced a dose-dependent increase in mean arterial blood pressure (MAP) and reduced renal blood flow (RBF) and glomerular filtration rate (GFR), when compared with an equivalent infusion of physiological saline. 2. Endothelin, 20 pmol kg-1 min-1, was also assessed in animals pretreated with either indomethacin (2 mg kg-1), methylene blue (1.6 mg kg-1 h-1) or NG-monomethyl L-arginine (L-NMMA, 10 mg kg-1 h-1). 3. The effect of endothelin on MAP and RBF was enhanced (P = 0.05 and < 0.01 respectively) by the cyclo-oxygenase inhibitor, indomethacin, without any significant change in the effect on GFR. 4. Methylene blue and L-NMMA, inhibitors of endothelium-derived relaxant factor (EDRF), enhanced the effect of endothelin on each of the parameters measured (P < 0.01). 5. Our results are consistent with endothelin having a predominant effect on pre-glomerular vascular resistance to reduce GFR. Endothelin appears to stimulate the release of vasodilator prostanoids and EDRF which oppose its effects. Thus endothelin may have an important role in the complex control of GFR in the rabbit.