Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
J Pharmacol Sci. 2012;119(2):122-30. doi: 10.1254/jphs.12058fp. Epub 2012 May 17.
Up-regulation of kidney α2-adrenoceptor expression has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). This study was carried out to evaluate renal sodium excretion in response to clonidine administration in SHR and control normotensive Wistar-Kyoto (WKY) rats. SHR and WKY rats (12-week-old) were placed in metabolic cages for 4 days: the first 2 days in control conditions and the following 2 days under oral clonidine treatment (100 μg/kg body weight). Clonidine produced a similar reduction in systolic blood pressure values in SHR and WKY rats, although SHR remained hypertensive. At the end of the study SHR and WKY rats presented similar noradrenaline plasma levels. However, noradrenaline kidney tissue levels were significantly higher in SHR compared to WKY rats. Under control conditions, SHR presented lower urine flow compared to WKY rats. Clonidine produced a significant decrease in urine flow in WKY rats but not in SHR. Furthermore, clonidine also produced a significant reduction in urinary sodium, potassium, and creatinine excretion in WKY rats, but had no effect in SHR. In conclusion, in SHR the reduction in systolic blood pressure and sympathetic activity produced by clonidine was not accompanied by a decrease in urine volume and sodium excretion.
肾脏α2-肾上腺素受体表达的上调与自发性高血压大鼠（SHR）高血压的发展有关。本研究旨在评估氯压定给药对 SHR 和对照正常血压 Wistar-Kyoto（WKY）大鼠的肾脏钠排泄的影响。将 SHR 和 WKY 大鼠（12 周龄）置于代谢笼中 4 天：前 2 天为对照条件，后 2 天进行口服氯压定（100μg/kg 体重）治疗。氯压定使 SHR 和 WKY 大鼠的收缩压值降低相似，但 SHR 仍保持高血压。在研究结束时，SHR 和 WKY 大鼠的去甲肾上腺素血浆水平相似。然而，与 WKY 大鼠相比，SHR 的肾组织去甲肾上腺素水平明显升高。在对照条件下，与 WKY 大鼠相比，SHR 的尿量较低。氯压定使 WKY 大鼠的尿量显著减少，但对 SHR 没有影响。此外，氯压定还使 WKY 大鼠的尿钠、钾和肌酐排泄量显著减少，但对 SHR 没有影响。总之，在 SHR 中，氯压定降低收缩压和交感神经活性并没有伴随着尿量和钠排泄的减少。
