Choisy Stéphanie C, Kim Shang-Jin, Hancox Jules C, Jones Sandra A, James Andrew F
Cardiovascular Research Laboratories, School of Physiology & Pharmacology, School of Medical Sciences, University of Bristol, Bristol, U.K.
Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju-City, South Korea.
Physiol Rep. 2015 Jan 27;3(1). doi: 10.14814/phy2.12274. Print 2015 Jan 1.
Hypertension-induced structural remodeling of the left atrium (LA) has been suggested to involve the renin-angiotensin system. This study investigated whether treatment with an angiotensin receptor blocker, candesartan, regresses atrial remodeling in spontaneously hypertensive rats (SHR). Effects of treatment with candesartan were compared to treatment with a nonspecific vasodilatator, hydralazine. Thirty to 32-week-old adult male SHR were either untreated (n = 15) or received one of either candesartan cilexetil (n = 9; 3 mg/kg/day) or hydralazine (n = 10; 14 mg/kg/day) via their drinking water for 14 weeks prior to experiments. Untreated age- and sex-matched Wistar-Kyoto rats (WKY; n = 13) represented a normotensive control group. Untreated SHR were hypertensive, with left ventricular hypertrophy (LVH) compared to WKY, but there were no differences in systolic pressures in excised, perfused hearts. LA from SHR were hypertrophied and showed increased fibrosis compared to those from WKY, but there was no change in connexin-43 expression or phosphorylation. Treatment with candesartan reduced systolic tail artery pressures of conscious SHR below those of normotensive WKY and caused regression of both LVH and LA hypertrophy. Although hydralazine reduced SHR arterial pressures to those of WKY and led to regression of LA hypertrophy, it had no significant effect on LVH. Notably, LA fibrosis was unaffected by treatment with either agent. These data show that candesartan, at a dose sufficient to reduce blood pressure and LVH, did not cause regression of LA fibrosis in hypertensive rats. On the other hand, the data also suggest that normalization of arterial pressure can lead to the regression of LA hypertrophy.
高血压引起的左心房（LA）结构重塑被认为与肾素-血管紧张素系统有关。本研究调查了血管紧张素受体阻滞剂坎地沙坦治疗是否能使自发性高血压大鼠（SHR）的心房重塑消退。将坎地沙坦治疗的效果与非特异性血管扩张剂肼屈嗪治疗的效果进行了比较。30至32周龄的成年雄性SHR要么不接受治疗（n = 15），要么在实验前14周通过饮用水接受坎地沙坦西酯（n = 9；3 mg/kg/天）或肼屈嗪（n = 10；14 mg/kg/天）治疗之一。未接受治疗的年龄和性别匹配的Wistar-Kyoto大鼠（WKY；n = 13）代表正常血压对照组。未接受治疗的SHR血压升高，与WKY相比有左心室肥厚（LVH），但在离体灌注心脏中收缩压没有差异。与WKY相比，SHR的LA肥厚且纤维化增加，但连接蛋白43的表达或磷酸化没有变化。坎地沙坦治疗可使清醒SHR的收缩期尾动脉压低于正常血压的WKY，并导致LVH和LA肥厚消退。虽然肼屈嗪可使SHR的动脉压降至WKY的水平，并导致LA肥厚消退，但对LVH没有显著影响。值得注意的是，两种药物治疗均未影响LA纤维化。这些数据表明，在足以降低血压和LVH的剂量下，坎地沙坦不会使高血压大鼠的LA纤维化消退。另一方面，数据还表明动脉压正常化可导致LA肥厚消退。
