Song Jin, Kost Curtis K, Martin Douglas S
Basic Biomedical Sciences, University of South Dakota, Vermillion SD 57069, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1608-15. doi: 10.1152/ajpregu.00364.2005. Epub 2006 Feb 9.
Males develop higher blood pressure than do females. This study tested the hypothesis that androgens enhance responsiveness to ANG II during the development of hypertension in New Zealand genetically hypertensive (NZGH) rats. Male NZGH rats were obtained at 5 wk of age and subjected to sham operation (Sham) or castration (Cas) then studied at three age groups: 6-7, 11-12, and 16-17 wk. Mean arterial blood pressure (MAP), heart rate (HR), and renal blood flow (RBF) measurements were recorded under Inactin anesthesia. These variables were measured after enalapril (1 mg/kg) treatment and during intravenous ANG II infusion (20, 40, and 80 ng/kg/min). Plasma testosterone was measured by ELISA. Angiotensin type 1 (AT1) receptor expression was assessed by Western blot analysis and RT-PCR. ANG II-induced MAP responses were significantly attenuated in Cas NZGH rats. At the highest ANG II dose, MAP increased by 40+/-4% in Sham vs. 22+/-1% in Cas NZGH rats of 16-17 wk of age. Similarly, renal vascular resistance (RVR) responses to ANG II were reduced by castration (209+/-20% in Sham vs. 168+/-10% in Cas NZGH rats at 16-17 wk of age). Castration also reduced MAP recorded in conscious NZGH rats of this age group. Testosterone replacement restored baseline MAP and the pressor and RVR responses to ANG II. Castration reduced testosterone concentrations markedly. Testosterone treatment restored these concentrations. Neither castration nor castration+testosterone treatment affected AT1 receptor mRNA or protein expression. Collectively, these data suggest that androgens modulate renal and systemic vascular responsiveness to ANG II, which may contribute to androgen-induced facilitation of NZGH rat hypertension.
雄性比雌性更容易患高血压。本研究检验了一种假说，即在新西兰遗传性高血压（NZGH）大鼠高血压发展过程中，雄激素会增强对血管紧张素II（ANG II）的反应性。雄性NZGH大鼠在5周龄时获取，进行假手术（Sham）或去势手术（Cas），然后在三个年龄组进行研究：6 - 7周、11 - 12周和16 - 17周。在氯胺酮麻醉下记录平均动脉血压（MAP）、心率（HR）和肾血流量（RBF）。在给予依那普利（1 mg/kg）治疗后以及静脉输注ANG II（20、40和80 ng/kg/min）期间测量这些变量。通过酶联免疫吸附测定法（ELISA）测量血浆睾酮。通过蛋白质印迹分析和逆转录-聚合酶链反应（RT-PCR）评估血管紧张素1（AT1）受体表达。在去势的NZGH大鼠中，ANG II诱导的MAP反应显著减弱。在最高ANG II剂量下，16 - 17周龄的假手术NZGH大鼠MAP升高40±4%，而去势的NZGH大鼠为22±1%。同样，去势降低了对ANG II的肾血管阻力（RVR）反应（16 - 17周龄时，假手术NZGH大鼠为209±20%，去势的NZGH大鼠为168±10%）。去势也降低了该年龄组清醒NZGH大鼠记录的MAP。睾酮替代恢复了基线MAP以及对ANG II的升压和RVR反应。去势显著降低了睾酮浓度。睾酮治疗恢复了这些浓度。去势和去势+睾酮治疗均未影响AT1受体mRNA或蛋白质表达。总体而言，这些数据表明雄激素调节肾脏和全身血管对ANG II的反应性，这可能有助于雄激素诱导的NZGH大鼠高血压的促进作用。
