Sanz Elena, Fernández Nuria, Monge Luis, Climent Belén, Diéguez Godofredo, García-Villalón Angel Luis
Departamento de Fisiologi;a, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo 2, 28029 Madrid, Spain.
Cardiovasc Res. 2003 Jun 1;58(3):706-11. doi: 10.1016/s0008-6363(03)00293-1.
Urocortin is a peptide structurally related to corticotropin releasing factor (CRF), and the present study was performed to examine the effects of diabetes mellitus on the relaxation by urocortin of renal arteries from males and females.
The response to urocortin was studied in isolated segments, 2 mm long, from renal arteries, from male and female, control (normoglycemic) and streptozotocin-induced diabetic rats.
In the renal arterial segments precontracted with endothelin-1, urocortin produced concentration-dependent relaxation, that was not different between males and females. Diabetes reduced the relaxation in renal arteries from females but not in those from males. The potassium channel blocker charybdotoxin (10(-7) M) reduced the relaxation to urocortin of renal arteries from normoglycemic males and females. The cyclooxygenase inhibitor meclofenamate did not modify the relaxation to urocortin in renal arteries from normoglycemic males or females. The inhibitor of nitric oxide synthesis N(W)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) reduced the relaxation to urocortin in renal arteries from normoglycemic females, but not in renal arteries from normoglycemic males. Neither charybdotoxin, L-NAME or meclofenamate modified the relaxation to urocortin of renal arteries from diabetic females.
These results suggest that urocortin produces a marked vasodilation of renal arteries, which may be mediated by nitric oxide in females and by activation of potassium channels in both genders, and is reduced by diabetes in renal arteries from females.
尿皮质素是一种在结构上与促肾上腺皮质激素释放因子(CRF)相关的肽,本研究旨在探讨糖尿病对尿皮质素舒张雄性和雌性大鼠肾动脉的影响。
研究了从雄性和雌性对照(血糖正常)大鼠及链脲佐菌素诱导的糖尿病大鼠的肾动脉中分离出的2毫米长的节段对尿皮质素的反应。
在内皮素-1预收缩的肾动脉节段中,尿皮质素产生浓度依赖性舒张,雄性和雌性之间无差异。糖尿病降低了雌性大鼠肾动脉的舒张,但对雄性大鼠肾动脉无影响。钾通道阻滞剂蝎毒素(10^-7 M)降低了血糖正常的雄性和雌性大鼠肾动脉对尿皮质素的舒张。环氧化酶抑制剂甲氯芬那酸未改变血糖正常的雄性或雌性大鼠肾动脉对尿皮质素的舒张。一氧化氮合成抑制剂N(W)-硝基-L-精氨酸甲酯(L-NAME,10^-4 M)降低了血糖正常的雌性大鼠肾动脉对尿皮质素的舒张,但对血糖正常的雄性大鼠肾动脉无影响。蝎毒素、L-NAME或甲氯芬那酸均未改变糖尿病雌性大鼠肾动脉对尿皮质素的舒张。
这些结果表明,尿皮质素可使肾动脉显著舒张,在雌性中可能由一氧化氮介导,在两性中均由钾通道激活介导,糖尿病可降低雌性大鼠肾动脉的舒张。