Different sensitivities of porcine coronary arteries and veins to BAY 60–2770, a soluble guanylate cyclase activator

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences Pub Date : 2024-11-14 DOI:10.1016/j.jphs.2024.11.002

Masashi Tawa, Keisuke Nakagawa, Mamoru Ohkita

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引用次数: 0

Abstract

Nitric oxide (NO)-donor drugs, which stimulate reduced form of soluble guanylate cyclase (sGC), have different efficacy to the arteries and veins. This study examined whether sGC activators, which activate oxidized/apo sGC, also have arteriovenous selectivity similar to that of NO-donor drugs. The mechanical responses of the isolated blood vessels were assessed using the organ chamber technique and protein expression was verified using western blotting. BAY 60–2770 (sGC activator) caused concentration-dependent relaxation in both porcine coronary arteries and veins, with the response being slightly more pronounced in the arteries. In contrast, sodium nitroprusside (NO-donor drug)-induced relaxation of the arteries was slightly weaker than that of the veins. Vasorelaxant responses to 8-Br-cGMP (cGMP analog) did not differ between the arteries and veins. In the presence of ODQ (heme oxidant), the heterogeneities in the responses to BAY 60–2770 and sodium nitroprusside between the arteries and veins disappeared. The sGC expression in the arteries did not differ from that in the veins. These findings suggest that sGC activators, in contrast to NO-donor drugs, have greater effects on the arteries than on the veins. This may be due to differences in the balance of sGC forms expressed in the arteries and veins.

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猪冠状动脉和静脉对可溶性鸟苷酸环化酶激活剂 BAY 60-2770 的不同敏感性

一氧化氮（NO）供体药物可刺激还原型可溶性鸟苷酸环化酶（sGC），但对动脉和静脉的疗效不同。本研究探讨了激活氧化型/apo型sGC的sGC激活剂是否也具有类似于一氧化氮供体药物的动静脉选择性。使用器官室技术评估了离体血管的机械反应，并使用 Western 印迹技术验证了蛋白质的表达。BAY 60-2770（sGC 激活剂）在猪冠状动脉和静脉中都能引起浓度依赖性松弛，在动脉中反应略微明显。相比之下，硝普钠（NO 供体药物）诱导的动脉松弛作用略弱于静脉松弛作用。动脉和静脉对 8-Br-cGMP（cGMP 类似物）的血管舒张反应没有差异。在 ODQ（血红素氧化剂）存在的情况下，动脉和静脉对 BAY 60-2770 和硝普钠反应的异质性消失了。动脉中的 sGC 表达与静脉中的没有差异。这些研究结果表明，与 NO 供体药物不同，sGC 激活剂对动脉的影响大于对静脉的影响。这可能是由于动脉和静脉中表达的 sGC 形式的平衡存在差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.