Mechanisms of increased venous smooth muscle tone in desoxycorticosterone acetate-salt hypertension
Mechanisms of increased venous smooth muscle tone in desoxycorticosterone acetate-salt hypertension
复制标题
DOI：
10.1161/01.hyp.35.1.464
复制
发表时间：
2000-01-01
期刊：
影响因子：
8.3
通讯作者：
Galligan, J
中科院分区：
文献类型：
--
作者：
Fink, GD;Johnson, RJ;Galligan, J
本研究的目的是确定机制，有助于增加静脉平滑肌张力醋酸脱氧皮质酮（DOCA）盐高血压大鼠。雄性Sprague-Dawley大鼠单侧肾切除，接受DOCA皮下植入，并饮用1%氯化钠/0.2%氯化钾溶液。假手术组大鼠只接受单侧肾切除术，并饮用自来水。3 - 4周后，植入动脉和静脉导管，分别测量动脉和中心静脉压，并将硅胶球囊导管永久固定在右心房，以产生短暂的循环停止。静脉平滑肌活动估计的基础上重复测量的平均循环充盈压;在清醒的大鼠休息，在他们的家笼。DOCA-盐处理的大鼠高血压和升高的平均循环充盈压与正常血压假手术大鼠相比。用1 mg/kg ABT-627 IV阻断内皮素亚型A受体，使高血压大鼠的动脉血压和平均循环充盈压显著低于正常血压大鼠。神经节阻滞与30毫克/公斤六甲双铵IV也降低动脉血压和平均循环充盈压高血压大鼠比正常血压大鼠。ABT-627预处理不影响随后对神经节阻滞的血流动力学反应。我们的结论是静脉平滑肌张力增加DOCA盐高血压通过内源性内皮素-1作用于亚型A受体和交感神经介导的静脉收缩活性的独立行动。
The purpose of the present study was to identify mechanisms that contribute to increased venous smooth muscle tone in desoxycorticosterone acetate (DOCA)-salt hypertension in rats. Male Sprague-Dawley rats were uninephrectomized, received subcutaneous implants of DOCA, and drank 1% sodium chloride/0.2% potassium chloride solutions. Sham-operated rats received only uninephrectomy and drank tap water. Three to 4 weeks later, arterial and venous catheters were implanted for measurements of arterial and central venous pressures, respectively, and a silicone balloon catheter was permanently fixed in the right atrium to produce brief circulatory arrest. Venous smooth muscle activity was estimated on the basis of repeated measurements of mean circulatory filling pressure; in conscious rats resting in their home cages. DOCA-salt-treated rats were hypertensive and had elevated mean circulatory filling pressure compared with normotensive sham-operated rats. Blockade of the endothelin subtype A receptor with 1 mg/kg ABT-627 IV decreased arterial blood pressure and mean circulatory filling pressure significantly more in hypertensive rats than in normotensive rats. Ganglionic blockade with 30 mg/kg hexamethonium IV also decreased arterial blood pressure and mean circulatory filling pressure more in hypertensive than in normotensive rats. Pretreatment with ABT-627 did not affect subsequent hemodynamic responses to ganglionic blockade. We conclude that venous smooth muscle tone is increased in DOCA-salt hypertension through the independent actions of both endogenous endothelin-1 acting on subtype A receptors and sympathetically mediated venoconstrictor activity.