Susic D, Varagic J, Frohlich E D
Hypertension Research Laboratory, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
J Hypertens. 1999 Aug;17(8):1209-15. doi: 10.1097/00004872-199917080-00022.
To determine whether antihypertensive treatment could alter hypertension and age-related progressive impairment of coronary hemodynamics and cardiac fibrosis in aged spontaneously hypertensive rats (SHR).
Old SHR were given their respective therapy for 3 months. To differentiate between hypertension and age-related changes, a comparison was made between left and right ventricular indices since the right ventricle was not exposed to pressure overload.
Male, 65-week-old spontaneously SHR were divided into three groups and were given either vehicle, felodipine (30 mg/kg per day) or enalapril (30 mg/kg per day). After 12 weeks of the respective treatments, systemic and coronary hemodynamics (radionuclide-labelled microspheres), right and left ventricular and aortic mass indices, and right and left ventricular hydroxyproline concentrations (an estimate of collagen) were determined.
Arterial pressure and total peripheral resistance were reduced to the same extent in SHRs treated with either felodipine or enalapril; however, compared to the control rats, enalapril was more effective in reducing left ventricular and aortic mass indices. Both agents also improved coronary hemodynamics of both ventricles in aged SHR but enalapril was more effective as indicated by a greater increase in coronary flow reserve and a greater decrease in minimal coronary vascular resistance. Furthermore, enalapril but not felodipine reduced left ventricular hydroxyproline concentration; and right ventricular hydroxyproline concentration increased with felodipine but remained unchanged with enalapril.
Both enalapril and felodipine ameliorated adverse cardiovascular effects of hypertension in the aged SHRs within 12 weeks, as demonstrated by reduced arterial pressure, diminished left ventricular mass, and improved coronary hemodynamics. Enalapril also decreased aortic mass and left ventricular collagen concentration and appeared to be more effective in improving coronary hemodynamics than felodipine, possibly as a result, in part, of reduced myocardial fibrosis.
确定抗高血压治疗是否能改变老年自发性高血压大鼠（SHR）的高血压以及与年龄相关的冠状动脉血流动力学和心脏纤维化的进行性损害。
对老年SHR进行各自的治疗，为期3个月。为区分高血压和与年龄相关的变化，由于右心室未承受压力过载，因此对左右心室指标进行了比较。
将65周龄的雄性自发性SHR分为三组，分别给予溶媒、非洛地平（每天30mg/kg）或依那普利（每天30mg/kg）。在进行各自治疗12周后，测定全身和冠状动脉血流动力学（放射性核素标记微球）、左右心室和主动脉质量指数，以及左右心室羟脯氨酸浓度（胶原蛋白的一种估计）。
用非洛地平或依那普利治疗的SHR，动脉压和总外周阻力降低程度相同；然而，与对照大鼠相比，依那普利在降低左心室和主动脉质量指数方面更有效。两种药物还改善了老年SHR两心室的冠状动脉血流动力学，但依那普利更有效，表现为冠状动脉血流储备增加更多，最小冠状动脉血管阻力降低更多。此外，依那普利降低了左心室羟脯氨酸浓度，而非洛地平未降低；右心室羟脯氨酸浓度随非洛地平升高，但依那普利治疗后保持不变。
非洛地平和依那普利均在12周内改善了老年SHR高血压的不良心血管效应，表现为动脉压降低、左心室质量减轻和冠状动脉血流动力学改善。依那普利还降低了主动脉质量和左心室胶原蛋白浓度，并且在改善冠状动脉血流动力学方面似乎比非洛地平更有效，这可能部分是由于心肌纤维化减轻所致。
