Ahmad Ashfaq, Sattar Munavvar, Khan Safia Akhtar, Abdullah Nor A, Johns Edward J, Afzal Samina
Acta Pol Pharm. 2017 Mar;74(2):413-423.
Present study explored endothelial nitric oxide synthase/nitric oxide (eNOS/NO) pathway in the kidney and role of αIB adrenergic receptor in the regulation of renal vasculature in the rats with left ventricular hypertrophy (LVH). LVH was induced by administering isoprenaline 5 mg/kg (s.c. 72 h. apart) and caffeine (62 mg/L in drinking water) for 14 days. Quantification of molecular expression of eNOS in kidney was performed by quantitative Real Time Polymerase Chain Reaction (qPCR). Renal vasoconstrictor responses were measured by administering noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) in pre-drug phase, low dose and high dose phases of chloroethylelonidine (CEC), a selective of (αIB adrenergic receptor antagonist. In the kidney of LVH male Wistar Kyoto (WKY) rats eNOS was significantly down regulated (p < 0.05) by 74% relative to Control WKY (taken as 100%). The high dose 5 CEC attenuated the vasoconstrictor responses to NA by 41%, PE by 43% and ME by 33% in the LVH-WKY when compared to the same dose phase in Control WKY group. In LVH, increased oxidative stress in kidney and increased ACE activity in the plasma resulted in down regulation of eNOS/NO in the kidney. The renal vasoconstrictor responses to adrenergic agonist are blunted in LVH and (αIB adrenergic receptor is functional subtype in renal vasculature in LVH.
本研究探讨了左心室肥厚（LVH）大鼠肾脏中的内皮型一氧化氮合酶/一氧化氮（eNOS/NO）途径以及α1B肾上腺素能受体在肾血管调节中的作用。通过皮下注射5mg/kg异丙肾上腺素（间隔72小时）和给予含62mg/L咖啡因的饮用水诱导LVH，持续14天。采用定量实时聚合酶链反应（qPCR）对肾脏中eNOS的分子表达进行定量分析。通过在氯乙拉尼定（CEC，一种α1B肾上腺素能受体拮抗剂）的给药前阶段、低剂量和高剂量阶段给予去甲肾上腺素（NA）、苯肾上腺素（PE）和甲氧明（ME）来测量肾血管收缩反应。在LVH雄性Wistar Kyoto（WKY）大鼠的肾脏中，eNOS相对于对照WKY大鼠（设为100%）显著下调74%（p<0.05）。与对照WKY组相同剂量阶段相比，高剂量CEC使LVH-WKY大鼠对NA的血管收缩反应减弱41%，对PE的减弱43%，对ME的减弱33%。在LVH大鼠中，肾脏氧化应激增加和血浆中ACE活性升高导致肾脏中eNOS/NO下调。LVH大鼠对肾上腺素能激动剂的肾血管收缩反应减弱，且α1B肾上腺素能受体是LVH大鼠肾血管中的功能性亚型。
