In vitro evidence that the vasorelaxant effects of 2-nitro-1-phenyl-1-propanol on rat coronary arteries involve cyclic nucleotide pathways.

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Alfredo Augusto Vasconcelos-Silva, Suliana Mesquita Paula, Karine Lima-Silva, Kalinne Kelly Lima de Gadelha, Rodrigo José Bezerra de Siqueira, Armenio Aguiar Dos Santos, Saad Lahlou, Ricardo de Freitas Lima, Pedro Jorge Caldas Magalhães
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引用次数: 0

Abstract

The synthetic nitro-alcohol 2-nitro-1-phenyl-1-propanol (NPP) has endothelium-independent relaxing properties in isolated preparations of rat aorta and mesenteric artery. In this study, we investigated whether the vasodilator effects occur in coronary vessels and explored whether hyperpolarization is involved in the underlying mechanism of NPP-induced smooth muscle relaxation. The relaxing responses were studied in isolated preparations of the left anterior descending coronary (ADC) and the septal coronary (SC) arteries, which had been previously maintained under sustained contraction induced by the thromboxane A2 analogue U-46619. Administered cumulatively, NPP elicited concentration-dependent vasorelaxation with similar potency in both vessels. The relaxant effect remained unaffected by the nitric oxide synthase inhibitor L-NAME, the protein kinase C inhibitor bisindolylmaleimide IV and the Rho-associated protein kinase inhibitor Y-27632. However, it was significantly diminished by the adenylyl cyclase inhibitor MDL-12,330A, the guanylyl cyclase inhibitor ODQ, as well as the K+ channel inhibitors tetraethylammonium and CsCl. In ADC preparations impaled with intracellular micropipettes, NPP hyperpolarized the vascular preparation. When the isolated preparation was precontracted by 5-hydroxytryptamine or 80 mM KCl, NPP-induced relaxation with lower pharmacological potency compared to the vessels contracted by U-46619. In conclusion, NPP exhibits vasorelaxant effects on rat coronary arteries, likely involving pathways that include cyclic nucleotide production and membrane hyperpolarization.

体外证据表明,2-硝基-1-苯基-1-丙醇对大鼠冠状动脉的血管舒张作用涉及环核苷酸途径。
合成硝基酒精 2-硝基-1-苯基-1-丙醇(NPP)在大鼠主动脉和肠系膜动脉离体制备物中具有不依赖于内皮的松弛特性。在这项研究中,我们探讨了冠状动脉血管中是否存在血管扩张效应,并探讨了超极化是否参与了 NPP 诱导平滑肌松弛的基本机制。我们在左前降支冠状动脉(ADC)和室间隔冠状动脉(SC)的离体制备物中研究了松弛反应,这些制备物之前一直处于血栓素 A2 类似物 U-46619 诱导的持续收缩状态下。累积给药后,NPP 在两种血管中都能引起浓度依赖性血管舒张,且效力相似。一氧化氮合酶抑制剂 L-NAME、蛋白激酶 C 抑制剂双吲哚马来酰亚胺 IV 和 Rho- 相关蛋白激酶抑制剂 Y-27632 均不会影响其松弛作用。然而,腺苷酸环化酶抑制剂 MDL-12,330A、鸟苷酸环化酶抑制剂 ODQ 以及 K+ 通道抑制剂四乙基铵和氯化铯则会明显减弱这种作用。在用细胞内微量移液管插入的 ADC 制备中,NPP 使血管制备超极化。当用 5-hydroxytryptamine 或 80 mM KCl 预收缩离体制剂时,NPP 诱导的松弛药效低于 U-46619 收缩的血管。总之,NPP 对大鼠冠状动脉具有血管舒张作用,可能涉及的途径包括环核苷酸生成和膜超极化。
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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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