肺动脉高压大鼠肺动脉制剂对血管舒张药物的反应。

Responses to vasodilator drugs on pulmonary artery preparations from pulmonary hypertensive rats.

作者信息

Wanstall J C, O'Donnell S R

机构信息

Department of Physiology and Pharmacology, University of Queensland, Australia.

出版信息

Br J Pharmacol. 1992 Jan;105(1):152-8. doi: 10.1111/j.1476-5381.1992.tb14227.x.

DOI:10.1111/j.1476-5381.1992.tb14227.x

PMID:1596677

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908596/

Abstract

Relaxant responses to six vasodilator drugs, with different mechanisms of action, were examined on noradrenaline (0.1 microM)-contracted ring preparations of pulmonary artery and aorta taken from rats with pulmonary hypertension induced by monocrotaline or chronic hypoxia. 2. On pulmonary artery preparations from monocrotaline-treated rats, compared with controls, (a) the maximum relaxation to pinacidil and cromakalim was significantly increased, but their potency (negative log EC50) was unchanged, (b) the potencies of nitroprusside and sodium nitrite were significantly reduced (10 fold and 3 fold respectively), but there was no change in the maxima, (c) for nicorandil there was an increase in maximum relaxation and a decrease in potency (3 fold), and (d) for atriopeptin II there was no change in potency or maximum. 3. The increase in maximum relaxation for pinacidil and the decrease in potency for nitroprusside were also demonstrated in pulmonary artery preparations from rats with chronic hypoxic pulmonary hypertension. The other four drugs were not examined in preparations from hypoxic rats. 4. In both models of pulmonary hypertension, no change in maximum response or potency was seen on aortic preparations for any of the vasodilator drugs. 5. In control preparations, none of the drugs was more potent on pulmonary artery than on aorta (i.e. they were not pulmonary-selective). In preparations from pulmonary hypertensive rats, pinacidil was selective for pulmonary artery, in contrast to nitroprusside which was selective for aorta.6. It is concluded that the development of pulmonary hypertension in rats is accompanied by changes in the responsiveness of the pulmonary arteries to some vasodilator drugs; whether or not these changes occur depends on the mechanism of action of the vasodilator drug, but they are independent of the method of inducing pulmonary hypertension.7. It is postulated that the reduction in potency seen for nitroprusside, sodium nitrite and nicorandil may be due to desensitization of soluble guanylate cyclase in pulmonary vascular smooth muscle in pulmonary hypertension.

摘要

研究了六种作用机制不同的血管舒张药物对取自用野百合碱或慢性低氧诱导的肺动脉高压大鼠的去甲肾上腺素（0.1微摩尔）收缩的肺动脉和主动脉环标本的舒张反应。2. 在野百合碱处理大鼠的肺动脉标本上，与对照组相比，（a）匹那地尔和克罗卡林的最大舒张显著增加，但它们的效价（负对数EC50）不变，（b）硝普钠和亚硝酸钠的效价显著降低（分别为10倍和3倍），但最大值无变化，（c）尼可地尔的最大舒张增加而效价降低（3倍），（d）心房肽II的效价和最大值均无变化。3. 在慢性低氧性肺动脉高压大鼠的肺动脉标本中也证实了匹那地尔最大舒张的增加和硝普钠效价的降低。另外四种药物未在低氧大鼠的标本中检测。4. 在两种肺动脉高压模型中，任何血管舒张药物对主动脉标本的最大反应或效价均未观察到变化。5. 在对照标本中，没有一种药物对肺动脉的作用比对主动脉更强（即它们没有肺选择性）。在肺动脉高压大鼠的标本中，匹那地尔对肺动脉具有选择性，而硝普钠则对主动脉具有选择性。6. 得出结论，大鼠肺动脉高压的发展伴随着肺动脉对某些血管舒张药物反应性的变化；这些变化是否发生取决于血管舒张药物的作用机制，但与诱导肺动脉高压的方法无关。7. 据推测，硝普钠、亚硝酸钠和尼可地尔效价降低可能是由于肺动脉高压时肺血管平滑肌中可溶性鸟苷酸环化酶脱敏所致。