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 (UNaV) 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 UNaV significantly only at the highest dose. Acetylcholine at 10(-7) M decreased the RVR (-19%, p less than 0.05) and increased UNaV (+177%, p less than 0.05). In contrast, a soluble guanylate cyclase inhibitor, methylene blue (MB; 10(-5) M), increased the RVF by 30% (p less than 0.05) and decreased UNaV by 48% (p less than 0.05). Pretreatment with MB significantly augmented the ET-induced renal vasoconstriction by about 80%. However, UNaV 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 UNaV. These results suggest that the vasoconstrictor, but not the antinatriuretic, activity of ET may be modified by the release of EDRF and prostacyclin.
Hirata
Y
Y
Second Department of Internal Medicine, University of Tokyo, Japan.
Matsuoka
H
H
Kimura
K
K
Sugimoto
T
T
Hayakawa
H
H
Suzuki
E
E
Sugimoto
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D009569:Nitric Oxide; D012964:Sodium