Altered renin release and propranolol potentiation of vasodilatory drug hypotension.
Altered renin release and propranolol potentiation of vasodilatory drug hypotension.
复制标题
改变肾素释放和普萘洛尔对血管舒张药物低血压的增强作用。
DOI：
--
复制
发表时间：
1975
影响因子：
15.9
通讯作者：
K. Keeton
中科院分区：
文献类型：
--
作者：
W. Pettinger;K. Keeton
血管舒张性降压药可引起低血压，伴有反射性心动过速、肾素释放、液体和电解质潴留。普萘洛尔可损害这种肾素释放。本文所述的研究旨在确定血管舒张药物诱导的肾素释放的血液动力学作用和普萘洛尔在两种动物模型中的抑制作用，即未麻醉的血压正常大鼠和未麻醉的遗传性高血压大鼠。在对血压正常大鼠的研究中，普萘洛尔削弱了肼苯哒嗪和米诺地尔引起的肾素释放和心动过速，并增强了它们的降压作用。另外两种针对肾素-血管紧张素系统的干预措施用于评价这种增强作用的机制。一种是通过肾切除术去除肾素来源，第二种是使用选择性血管紧张素拮抗剂saralasin（1-Sar-8-Ala-血管紧张素II（以前称为P113））阻断血管紧张素的血管收缩作用。这两种干预措施加强血管舒张性药物低血压，普萘洛尔，但没有防止反射性心动过速。当与saralasin普萘洛尔结合时，没有增加这种肽的protentiation。当普萘洛尔或沙拉嗪先于肼苯哒嗪治疗时，在遗传性高血压大鼠中观察到类似的血压降低和增强模式。在遗传性高血压大鼠中，普萘洛尔被证明可以阻断肼苯哒嗪诱导的血清肾素活性增加。我们的结论是，在这些动物模型中，普萘洛尔对血管扩张药物的增强作用在很大程度上是通过损害肾素释放来介导的。在正常血压大鼠中，肾切除术后和saralasin后持续的扩张性心动过速表明血管紧张素的中枢神经系统刺激与这种心脏效应无关。临床研究正在进行中，以量化这种有益的药物相互作用在人体中的潜在重要性。
Vasodilating antihypertensive drugs induce hypotension with reflex tachycardia, renin release, and fluid and electrolyte retention. Propranolol can impair this renin release. The studies described here were designed to determine the hemodynamic role of vasodilatory drug-induced renin release and inhibition thereof by propranolol in two animals models, the unanesthetized, normotensive and the unanesthetized, genetically hypertensive rat. In studies with normotensive rats, propranolol impaired renin release and tachycardia resulting from hydralazine and minoxidil and potentiated their hypotensive action. Two additional interventions against the renin-angiotensin system were used in evaluating the mechanism of this potentiation. One was removal of the renin source by nephrectomy, and the second was blockade of angiotensin's vasoconstrictor action using a selective angiotensin antagonist, saralasin (1-Sar-8-Ala-angiotensin II (previously known as P113)).. Both interventions potentiated vasocilatory drug hypotension, as did propranolol, but did not prevent reflex tachycardia. When combined with saralasin propranolol did not add to protentiation by this peptide. A similar pattern of blood pressure decrement and potentiation was seen in genetically hypertensive rats when propranolol or saralasin treatment preceded hydralazine. Propranolol was demonstrated to block hydralazine-induced increases in serum renin activity in genetically hypertensive rats. We conclude that hypotensive potentiation of vasocilating drugs by propranolol in these animal models is mediated to a large extent by impairment of renin release. Persistence of hypotensive tachycardia after nephrectomy and after saralasin in normotensive rats suggests the irrelevance of angiotensin's central nervous system stimulation to this cardiac effect. Clinical studies are underway to quantify the potential importance of this beneficial drug interaction in man.