Marrachelli Vannina G, Miranda Francisco J, Alabadí José A, Lloréns Silvia, Alborch Enrique
Departamento de Fisiología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
Eur J Pharmacol. 2006 Mar 18;534(1-3):178-86. doi: 10.1016/j.ejphar.2006.01.043.
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.
研究了糖尿病对离体兔肾动脉对内皮素-1反应中涉及的调节机制和特定受体的影响。内皮素-1诱导浓度依赖性收缩，糖尿病兔动脉中的收缩作用比对照兔动脉中的弱。去除内皮或使用N(G)-硝基-L-精氨酸（L-NOARG）可增强对照和糖尿病动脉对内皮素-1的收缩反应。吲哚美辛抑制对照动脉中内皮素-1诱导的反应，但增强糖尿病动脉中的反应。与在rubbed和L-NOARG处理的动脉中观察到的情况相反，在吲哚美辛存在下，内皮素-1在糖尿病动脉中的收缩作用高于对照动脉。尼美舒利增强对照和糖尿病动脉中内皮素-1的收缩反应。环-（D-天冬氨酸-脯氨酸-D-缬氨酸-亮氨酸-D-色氨酸）（BQ-123，内皮素ET(A)受体拮抗剂）减弱对照兔中内皮素-1的血管收缩作用，而在糖尿病兔中血管收缩作用增强。2,6-二甲基哌啶羰基-γ-甲基-亮氨酸-N(in)-（甲氧基羰基）-D-色氨酸-D-正亮氨酸（BQ-788，内皮素ET(B)受体拮抗剂）增强对照兔动脉中的收缩反应，而对糖尿病兔的这种反应无影响。总之，糖尿病通过降低内皮素ET(A)受体激活后释放的血管收缩和血管舒张前列腺素之间的比例，降低兔肾动脉对内皮素-1的敏感性。
