Contribution of endothelin receptors and cyclooxygenase-derivatives to the altered response of the rabbit renal artery to endothelin-1 in diabetes.
The influence of diabetes on regulatory mechanisms and specific receptors implicated in the response of isolated rabbit renal artery to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was less potent in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or N(G)-nitro-L-arginine (L-NOARG) enhanced contractions to endothelin-1 either in control and diabetic arteries. Indomethacin inhibited endothelin-1-induced response in control arteries, but enhanced it in diabetic arteries. In contrast to that observed in rubbed and in L-NOARG treated arteries, in the presence of indomethacin the contractile action of endothelin-1 was higher in diabetic arteries than in control arteries. Nimesulide enhanced endothelin-1 contractions both in control and diabetic arteries. Cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123, endothelin ET(A) receptor antagonist), attenuated endothelin-1 vasoconstriction in control rabbits, while vasoconstriction resulted increased in diabetic rabbits. 2,6-Dimethylpiperidinecarbonyl-gamma-Methyl-Leu-N(in)-(Methoxycarbonyl)-D-Trp-D-Nle (BQ-788, endothelin ET(B) receptor antagonist), enhanced the contractile response in control rabbit arteries without modifying this response in diabetic rabbits. In summary, diabetes decreases the sensitivity of the rabbit renal artery to endothelin-1 by decreasing the ratio between vasoconstrictor and vasodilator prostanoids released after activation of endothelin ET(A) receptors.
Marrachelli
Vannina G
VG
Departamento de Fisiología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
Miranda
Francisco J
FJ
Alabadí
José A
JA
Lloréns
Silvia
S
Alborch
Enrique
E
D000496:Alloxan; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D044022:Receptor, Endothelin A / Q000187:drug effects* / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D014661:Vasoconstriction
D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D019335:Nitroarginine; D000496:Alloxan; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D007213:Indomethacin