Reckelhoff J F, Zhang H, Srivastava K
Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Hypertension. 2000 Jan;35(1 Pt 2):480-3. doi: 10.1161/01.hyp.35.1.480.
Previous data strongly support a role for androgens in promoting the gender difference in hypertension in the spontaneously hypertensive rat(s) (SHR), but the mechanism is not clear. Because males develop higher blood pressures than do females, we hypothesize that androgens may affect the renin-angiotensin system to promote the development of hypertension in male SHR. The present study was performed to determine the effect of converting enzyme inhibition (CEI) on the development of hypertension in SHR. Male, female, castrated male, and ovariectomized (ovx) female SHR (n=10 per gender per treatment group) received enalapril (250 mg/L) in drinking water for 8 to 10 weeks. Some ovx females were also given testosterone chronically. At 17 to 19 weeks of age, 24-hour protein excretion and mean arterial pressure were measured. By 13 weeks of age, male rats had higher systolic blood pressures by tail plethysmography than did the other rats, and CEI reduced blood pressures to similar levels in all groups. At 17 to 19 weeks, the same trend was found by direct measurement of mean arterial pressure. The ovx females treated with testosterone had serum testosterone and blood pressure levels similar to those found in males. CEI reduced mean arterial pressure to similar levels in all gender groups. Untreated males and ovx females given testosterone had significantly higher levels of urinary protein excretion than did the other groups, and CEI had no effect on proteinuria in any of the rats. These data suggest that the development of hypertension in SHR regardless of sex steroids is mediated by the renin-angiotensin system. However, the data further suggest that androgens promote the exacerbation of hypertension in male SHR via a mechanism involving the renin-angiotensin system.
既往数据有力地支持雄激素在自发性高血压大鼠（SHR）中促进高血压性别差异方面发挥作用，但机制尚不清楚。由于雄性大鼠的血压高于雌性，我们推测雄激素可能影响肾素-血管紧张素系统，从而促进雄性SHR高血压的发展。本研究旨在确定转换酶抑制（CEI）对SHR高血压发展的影响。雄性、雌性、去势雄性和卵巢切除（ovx）雌性SHR（每个性别每个治疗组n = 10）饮用含依那普利（250 mg/L）的水8至10周。一些ovx雌性大鼠还长期给予睾酮。在17至19周龄时，测量24小时尿蛋白排泄量和平均动脉压。到13周龄时，通过尾容积描记法测量，雄性大鼠的收缩压高于其他大鼠，CEI使所有组的血压降至相似水平。在17至19周时，通过直接测量平均动脉压也发现了相同的趋势。接受睾酮治疗的ovx雌性大鼠的血清睾酮和血压水平与雄性大鼠相似。CEI使所有性别组的平均动脉压降至相似水平。未治疗的雄性大鼠和给予睾酮的ovx雌性大鼠的尿蛋白排泄水平显著高于其他组，CEI对任何大鼠的蛋白尿均无影响。这些数据表明，无论性类固醇如何，SHR高血压的发展均由肾素-血管紧张素系统介导。然而，数据进一步表明，雄激素通过涉及肾素-血管紧张素系统的机制促进雄性SHR高血压的加重。
