Pendergrass Karl D, Pirro Nancy T, Westwood Brian M, Ferrario Carlos M, Brosnihan K Bridget, Chappell Mark C
Hypertension & Vascular Disease Ctr., Wake Forest Univ. Health Sciences, Winston-Salem, NC 27157-1095, USA.
Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H10-20. doi: 10.1152/ajpheart.01277.2007. Epub 2008 May 2.
Sex differences in blood pressure are evident in experimental models and human subjects, yet the mechanisms underlying this disparity remain equivocal. The current study sought to define the extent of male-female differences in the circulating and tissue renin-angiotensin aldosterone systems (RAASs) of congenic mRen(2). Lewis and control Lewis rats. Male congenics exhibited higher systolic blood pressure than females [200 +/- 4 vs. 146 +/- 7 mmHg, P < 0.01] or Lewis males and females [113 +/- 2 vs. 112 +/- 2 mmHg, P > 0.05]. Plasma ANG II levels were twofold higher in male congenics [47 +/- 3 vs. 19 +/- 3 pM, P < 0.01] and fivefold higher than in male or female Lewis rats [6 +/- 1 vs. 6 +/- 1 pM]. ANG I levels were also highest in the males; however, plasma ANG-(1-7) was higher in female congenics. Male congenics exhibited greater circulating renin and angiotensin-converting enzyme (ACE) activities, as well as angiotensinogen, than female littermates. Renal cortical and medullary ANG II levels were also higher in the male congenics versus all the other groups; ANG I was lower in the males. Cortical ACE2 activity was higher in male congenics, yet neprilysin activity and protein were greater in the females, which may contribute to reduced renal levels of ANG II. These data reveal that sex differences in both the circulating and renal RAAS are apparent primarily in the hypertensive group. The enhanced activity of the RAAS in male congenics may contribute to the higher pressure and tissue injury evident in the strain.
血压的性别差异在实验模型和人类受试者中都很明显，但这种差异背后的机制仍不明确。本研究旨在确定同基因mRen(2).Lewis大鼠和对照Lewis大鼠的循环及组织肾素 - 血管紧张素 - 醛固酮系统（RAASs）中雌雄差异的程度。同基因雄性大鼠的收缩压高于雌性[200±4 vs. 146±7 mmHg，P<0.01]，也高于Lewis雄性和雌性大鼠[113±2 vs. 112±2 mmHg，P>0.05]。雄性同基因大鼠的血浆ANG II水平高出两倍[47±3 vs. 19±3 pM，P<0.01]，比Lewis雄性或雌性大鼠高出五倍[6±1 vs. 6±1 pM]。ANG I水平在雄性中也最高；然而，雌性同基因大鼠的血浆ANG-(1-7)更高。雄性同基因大鼠的循环肾素和血管紧张素转换酶（ACE）活性以及血管紧张素原均高于同窝雌性大鼠。与所有其他组相比，雄性同基因大鼠的肾皮质和髓质ANG II水平也更高；雄性的ANG I水平较低。雄性同基因大鼠的皮质ACE2活性较高，但雌性的中性内肽酶活性和蛋白含量更高，这可能导致肾脏ANG II水平降低。这些数据表明，循环和肾脏RAAS中的性别差异主要在高血压组中明显。雄性同基因大鼠中RAAS活性增强可能导致该品系中明显的更高血压和组织损伤。
