Chen Y F, Yang R H, Meng Q C, Cragoe E J, Oparil S
Department of Medicine, University of Alabama at Birmingham 35294.
Am J Med Sci. 1994 Sep;308(3):145-51. doi: 10.1097/00000441-199409000-00004.
The current study was designed to determine the role of sodium-proton (Na+/H+) exchange in blood pressure regulation in sodium chloride (NaCl)-sensitive and NaCl-resistant spontaneously hypertensive rats and control Wistar-Kyoto rats (WKY) using 5-(N,N-hexamethylene)amiloride (HMA), a potent and selective inhibitor of Na+/H+ exchange. The response of mean arterial pressure to intravenous infusion of HMA was examined in conscious, unrestrained male rats maintained on normal (1%) or high (8%) NaCl diets for 3 weeks beginning at age 7 weeks. The HMA significantly increased mean arterial pressure in NaCl-sensitive spontaneously hypertensive rats and NaCl-resistant spontaneously hypertensive rats that were fed 1% NaCl, but not in WKY rats that were fed 1% NaCl; the 8% NaCl diet enhanced this pressor response in all 3 strains. The pressor response was accompanied by significant increases in plasma norepinephrine levels in NaCl-sensitive spontaneously hypertensive rats on both diets, but not in NaCl-resistant spontaneously hypertensive rats or WKY rats on either diet. There were no differences in steady-state levels (30-60 nM) of plasma HMA between diet groups in any strain. Therefore, administration of HMA in a dose at which it is highly selective for the Na+/H+ exchanger (Ki = 160 nM) caused a systemic pressor response in spontaneously hypertensive rats that was enhanced by dietary NaCl supplementation. With these data, it is suggested that inhibition of Na+/H+ exchange in vivo has a pressor effect greater in spontaneously hypertensive rats than in WKY rats and is further enhanced by NaCl supplementation.
本研究旨在利用5-(N,N-六亚甲基)氨氯吡脒（HMA，一种强效且选择性的钠-质子（Na+/H+）交换抑制剂），确定Na+/H+交换在氯化钠（NaCl）敏感型和NaCl抵抗型自发性高血压大鼠以及对照Wistar-Kyoto大鼠（WKY）血压调节中的作用。在7周龄开始的3周内，对自由活动的雄性大鼠静脉注射HMA，观察其平均动脉压的反应，这些大鼠分别维持在正常（1%）或高（8%）NaCl饮食。HMA显著升高了喂食1% NaCl的NaCl敏感型自发性高血压大鼠和NaCl抵抗型自发性高血压大鼠的平均动脉压，但对喂食1% NaCl的WKY大鼠无此作用；8% NaCl饮食增强了所有3个品系的这种升压反应。在两种饮食条件下，NaCl敏感型自发性高血压大鼠的升压反应均伴有血浆去甲肾上腺素水平显著升高，但NaCl抵抗型自发性高血压大鼠或WKY大鼠在任何一种饮食条件下均未出现这种情况。在任何品系中，不同饮食组之间血浆HMA的稳态水平（30 - 60 nM）均无差异。因此，以对Na+/H+交换器具有高度选择性的剂量（Ki = 160 nM）给予HMA，会在自发性高血压大鼠中引起全身升压反应，且这种反应会因补充饮食中的NaCl而增强。基于这些数据，提示体内抑制Na+/H+交换在自发性高血压大鼠中产生的升压作用比在WKY大鼠中更大，并且会因补充NaCl而进一步增强。
