Renal microvascular effects of endothelin.
The effects of endothelin 1, 2, and 3 (ET-1, -2, -3) on lumen diameter of individual afferent and efferent arterioles dissected from rabbit kidney were examined. ET-1 produced concentration-dependent and long-lasting decreases in lumen diameter in both arterioles. The 50% maximum response (EC50) values were 1.4 +/- 0.41 and 0.9 +/- 0.65 nM for afferent and efferent arterioles, respectively. In afferent arterioles, ET-2 produced decreases in lumen diameter (EC50 = 3.3 +/- 1.75 nM) that were indistinguishable from ET-1. However, ET-3 was considerably less potent (EC50 = 21.9 +/- 6.0 nM, P less than 0.05) than ET-1 or ET-2. Similar results were obtained in the efferent arteriole in which the EC50 for ET-2 (0.25 +/- 0.1 nM) was similar to ET-1, but ET-3 was significantly less potent (EC50 = 2.6 +/- 0.4 nM, P less than 0.05). Nicardipine (0.01-1 microM) produced concentration-dependent shifts in the ET-1 concentration-response curve in afferent arterioles. Verapamil (1 microM) also caused a significant shift in the ET-1 response curve. The contractile response to ET-1 was significantly more sensitive to nicardipine than was the response to norepinephrine. In contrast, the response of efferent arterioles to ET-1 and norepinephrine was unaffected by nicardipine or verapamil. The results demonstrate that ETs are potent vasoconstrictors of both the pre- and postglomerular microvasculature and may play a role in the regulation of renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
R M
RM
Edwards
W
W
Trizna
E H
EH
Ohlstein
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D016232:Endothelins; D010455:Peptides; D014700:Verapamil; D009529:Nicardipine