ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR IN ENDOTHELIN-INDUCED RENAL VASOCONSTRICTION

It has been suggested that endothelin (ET) induces the release of endothelium-derived relaxing factor (EDRF). To explore the possible modification of ET-induced renal vasoconstriction by EDRF, we examined the effects of ET on renal vascular resistance (RVR) and urinary Na excretion (U(Na) V) in the rat isolated perfused kidney before and after the administration of EDRF antagonists. ET at 2 x 10(-11) to 2 x 10(-9) M elevated the RVR in a dose-dependent fashion, whereas it lowered the RVR at 10(-12) M. ET decreased U(Na) V significantly only at the highest dose. Acetylcholine at 10(-7) M decreased the RVR (-19%, p < 0.05) and increased U(Na) V (+ 177%, p < 0.05). In contrast, a soluble guanylate cyclase inhibitor, methylene blue (MB; 10(-5) M), increased the RVR by 30% (p < 0.05) and decreased U(Na) V by 48% (p < 0.05). Pretreatment with MB significantly augmented the ET-induced renal vasoconstriction by about 80%. However, U(Na) V was not influenced significantly. ET increased the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1-alpha. Pretreatment with indomethacin (10(-5) M) also significantly enhanced the response of RVR to ET by 60% without changing U(Na) V. These results suggest that the vasoconstrictor, but not the antinatriuretic, activity of ET may be modified by the release of EDRF and prostacyclin.