α-人心房利钠肽（ANP）与沙丁胺醇、硝普钠和硝酸异山梨酯在人支气管平滑肌中的相互作用。

The interaction of alpha-human atrial natriuretic peptide (ANP) with salbutamol, sodium nitroprusside and isosorbide dinitrate in human bronchial smooth muscle.

作者信息

Nally J E, Clayton R A, Thomson N C, McGrath J C

机构信息

Autonomic Physiology Unit, Glasgow University.

出版信息

Br J Pharmacol. 1994 Dec;113(4):1328-32. doi: 10.1111/j.1476-5381.1994.tb17143.x.

DOI:10.1111/j.1476-5381.1994.tb17143.x

PMID:7889288

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1510526/

Abstract

Contractions in human bronchial rings evoked by methacholine (10(-6) M) were reversed by single contractions of alpha-human atrial natriuretic peptide (10(-6) M), salbutamol (10(-6) M), sodium nitroprusside (10(-6) M) or isosorbide dinitrate (4.2 x 10(-5) M) and the extent of the relaxations compared. The activity of combinations of ANP with salbutamol, sodium nitroprusside and isosorbide dinitrate were compared with those for each agonist alone. 2. ANP and salbutamol were equipotent in reversing methacholine-evoked contraction and, in combination these agonists evoked an additive response. ANP and sodium nitroprusside also evoked similar degrees of relaxation and were additive, as were ANP and isosorbide dinitrate; however, with isosorbide dinitrate a higher concentration was required to evoke the same degree of relaxation as ANP, sodium nitroprusside or salbutamol. 3. Cumulative concentration-response curves to methacholine (10(-9)-3 x 10(-4) M) were examined in the presence and absence of the above bronchodilator substances, alone and in combination allowing their abilities to protect against contraction to be compared. ANP (10(-6) M) and salbutamol (10(-6) M) each attenuated subsequent contractions evoked by methacholine, an ability not shared with sodium nitroprusside (10(-6) M) or isosorbide dinitrate (4.2 x 10(-5) M). Indeed at lower concentrations of methacholine (< 3 x 10(-7) M), sodium nitroprusside evoked a paradoxical enhancement of methacholine-evoked contractions. 4. In combination, ANP and salbutamol attenuated contractions evoked by methacholine to a significantly greater degree than that seen with either agonist alone, whilst a combination of ANP and sodium nitroprusside evoked no greater effect than that seen with ANP alone. By contrast, isosorbide dinitrate and ANP together evoked a greater inhibition than ANP alone.5 These results suggest that a combination of agents such as ANP and salbutamol evokes a greater effect than either alone, both in reversing and protecting against methacholine-evoked contractions.Such combinations may be of benefit in the treatment of patients, allowing lower doses of drug to be used. Combinations of ANP and isosorbide dinitrate may likewise be of interest; however, the mechanism underlying the enhancement of ANP responses by isosorbide dinitrate requires further study.

摘要

用10⁻⁶M的乙酰甲胆碱诱发的人支气管环收缩，可被10⁻⁶M的α-人心房利钠肽、沙丁胺醇、硝普钠或二硝酸异山梨酯单次收缩逆转，并比较松弛程度。比较了心房利钠肽与沙丁胺醇、硝普钠和二硝酸异山梨酯联合使用时的活性与每种激动剂单独使用时的活性。2. 心房利钠肽和沙丁胺醇在逆转乙酰甲胆碱诱发的收缩方面效力相当，联合使用时这些激动剂产生相加反应。心房利钠肽和硝普钠也产生相似程度的松弛且具有相加性，心房利钠肽和二硝酸异山梨酯也是如此；然而，与心房利钠肽、硝普钠或沙丁胺醇相比，二硝酸异山梨酯需要更高的浓度才能产生相同程度的松弛。3. 在有和没有上述支气管扩张物质存在的情况下，单独或联合检测对乙酰甲胆碱（10⁻⁹ - 3×10⁻⁴M）的累积浓度-反应曲线，可以比较它们预防收缩的能力。10⁻⁶M的心房利钠肽和10⁻⁶M的沙丁胺醇各自减弱了随后由乙酰甲胆碱诱发的收缩，硝普钠（10⁻⁶M）或二硝酸异山梨酯（4.2×10⁻⁵M）则没有这种能力。实际上，在较低浓度的乙酰甲胆碱（<3×10⁻⁷M）时，硝普钠会反常地增强乙酰甲胆碱诱发的收缩。4. 联合使用时，心房利钠肽和沙丁胺醇减弱乙酰甲胆碱诱发的收缩的程度明显大于单独使用任何一种激动剂时的情况，而心房利钠肽和硝普钠联合使用产生的效果并不比单独使用心房利钠肽时更大。相比之下，二硝酸异山梨酯和心房利钠肽一起使用时产生的抑制作用比单独使用心房利钠肽时更大。5. 这些结果表明，心房利钠肽和沙丁胺醇等药物联合使用在逆转和预防乙酰甲胆碱诱发的收缩方面比单独使用任何一种药物产生的效果更好。这种联合用药可能对患者治疗有益，可允许使用更低剂量的药物。心房利钠肽和二硝酸异山梨酯的联合使用同样可能有意义；然而，二硝酸异山梨酯增强心房利钠肽反应的潜在机制需要进一步研究。