Depressed Function of a Ouabain‐Sensitive Sodium‐Potassium Pump in Blood Vessels from Renal Hypertensive Dogs
Depressed Function of a Ouabain‐Sensitive Sodium‐Potassium Pump in Blood Vessels from Renal Hypertensive Dogs
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肾性高血压犬血管中哇巴因敏感钠钾泵功能的抑制
DOI：
10.1161/01.res.38.6.48
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发表时间：
1976
影响因子：
20.1
通讯作者：
F. Haddy
中科院分区：
文献类型：
--
作者：
H. W. Overbeck;M. Pamnani;T. Akera;T. Brody;F. Haddy
慢性单肾肾周性高血压犬、慢性双肾Goldblatt高血压大鼠和原发性高血压男性对急性动脉内输注K+的血管扩张剂反应减弱。有证据表明，K+通过刺激血管平滑肌膜Na+-K+活化的腺苷三磷酸酶引起血管舒张，从而增加细胞Na+-K+电致泵的活性。因此，我们提出高血压患者血管平滑肌中这种泵的运作可能存在潜在的减少。细胞Na+-K+泵的工作可以通过测量铷的摄取来估计。因此，为了进一步验证我们的假设，我们测量了12只患有慢性无并发症单肾肾周性高血压的狗和12只血压正常的对照组狗的肠系膜小动脉和肠腔静脉中86Rb的摄取。在硫胺醛麻醉下切除血管，在冷培养基（血浆或Krebs-Henseleit溶液）中培养钠负荷，然后在没有或存在瓦巴因（一种Na+-K+泵的特异性抑制剂）的情况下估计8SRb摄取的速度。在动脉和静脉中，没有证据表明高血压患者和正常血压患者在对瓦巴因不敏感的86Rb摄取方面存在差异。相比之下，高血压犬在自身血浆中孵育后，动脉和静脉对瓦他因敏感的86Rb摄取分别下降42% （P < 0.05）和49% （P < 0.01）。这些结果表明，慢性单肾肾周性高血压狗血管组织中钠钾离子敏感泵的活性可能受到抑制。因为血管平滑肌中的Na+-K+泵可能是电致的，这种异常，通过部分地使肌肉细胞膜去极化，将有助于解释在这些狗身上发现的血管阻力升高。
Vasodilator responses to acute intra-arterial infusions of K+ are attenuated in dogs with chronic one-kidney perinephritic hypertension in rats with chronic two-kidney Goldblatt hypertension, and in men with essential hypertension. There is evidence that K+ evokes vasodilation by stimulating vascular smooth muscle membrane Na+-K+-activated adenosine triphosphatase, thereby increasing activity of the cellular Na+-K+ electrogenic pump. We therefore proposed that there may be an underlying decrease in the operation of this pump in vascular smooth muscle of hypertensives. The operation of the cellular Na+-K+ pump may be estimated by measurement of rubidium uptake. Thus, to further investigate our hypothesis, we measured 86Rb uptake in small mesenteric arteries and splanchnic veins from 12 dogs with chronic uncomplicated one-kidney perinephritic hypertension and from 12 normotensive control dogs. Vessels were excised under thiamylal anesthesia and incubated in cold medium (plasma or Krebs-Henseleit solution) for sodium loading and then the velocity of 8SRb uptake was estimated in the absence of or in the presence of ouabain, a specific inhibitor of the Na+-K+ pump. In neither arteries nor veins was there evidence for differences between hypertensives and normotensives in the ouabain-insensitive uptake of 86Rb. In contrast, the ouabain-sensitive 86Rb uptake was depressed by 42% in arteries (P < 0.05) and by 49% in veins (P < 0.01) from hypertensive dogs, if incubated in the dog's own plasma. These results indicate that the activity of a ouabain-sensitive Na+-K+ pump may be depressed in vascular tissue from dogs with chronic one-kidney perinephritic hypertension. Because the Na+-K+ pump in vascular smooth muscle is probably electrogenic, such an abnormality, by partially depolarizing the muscle cell membrane, would help to account for the elevated vascular resistance found in these dogs.