Endothelin-1-induced contraction is impaired in the tail artery of renal hypertensive rats.
The contraction induced by endothelin-1 (ET-1) was evaluated in tail arteries from normotensive two-kidney (2K) and hypertensive two-kidney-one-clip (2K-1C) rats. Since the maximal effect induced by ET-1 (0.1-30 or 100 nmol/l) was lower in 2K-1C (1.11 +/- 0.10 g) than in 2K (1.46 +/- 0.14 g) tail arteries, we evaluated the possible mechanisms involved in this blunted response. The sensitivity and efficacy of ET-1 were not affected by endothelium removal in either group. ET-1 failed to induce contraction of 2K and 2K-1C arteries in Ca(2+)-free medium. The contractile response induced by 10 nmol/l ET-1 was similarly inhibited by 0.1 microM nifedipine in arteries from 2K (81.6 +/- 3.3%) and 2K-1C (81.3 +/- 3.8%) rats. The effect of nifedipine was not potentiated by 10 mumol/l SK&F 96365. The cytosolic Ca2+ concentration ([Ca2+]c) was similarly increased by 30 nmol/l ET-1 in smooth muscle cells isolated from tail arteries of 2K (30.80 +/- 11.94 nmol/l) and 2K-1C (54.06 +/- 10.98 nmol/l) rats. In conclusion, the blunted contraction induced by ET-1 in 2K-1C tail arteries was not dependent on the endothelium or on decreased Ca2+ influx through channels sensitive to nifedipine or SK&F 96365. Since the increase of [Ca2+]c upon stimulation with ET-1 was similar in 2K and 2K-1C tail artery cells, probably the sensitivity to Ca2+ is decreased in 2K-1C tail arteries.
Linder
Aurea Elizabeth
AE
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão, Preto, University of São Paulo, 14040-903 Ribeirão Preto, São Paulo, Brazil.
Bendhack
Lusiane Maria
LM
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply* / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D019332:Endothelin-1; D002118:Calcium