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

Journal Article · 04 October 2024 · Fundamental and Clinical Pharmacology

DOI: https://doi.org/10.1111/fcp.13038 · OSTI ID:2458248

Vasconcelos‐Silva, Alfredo Augusto ^[1]; Paula, Suliana Mesquita ^[1]; Lima‐Silva, Karine ^[1]; de Gadelha, Kalinne Kelly Lima ^[1]; de Siqueira, Rodrigo José Bezerra ^[1]; dos Santos, Armenio Aguiar ^[1]; Lahlou, Saad  ^[1]; de Freitas Lima, Ricardo ^[1]; Magalhães, Pedro Jorge Caldas  ^[1]

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1. Department of Physiology and Pharmacology, School of Medicine Federal University of Ceará Fortaleza Brazil

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 A ₂ 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.

• Sponsoring Organization: USDOE
• OSTI ID: 2458248
• Journal Information: Fundamental and Clinical Pharmacology, Journal Name: Fundamental and Clinical Pharmacology Journal Issue: 1 Vol. 39; ISSN 0767-3981
• Publisher: Wiley-BlackwellCopyright Statement
• Country of Publication: France
• Language: English