NONO2P, a nitric oxide donor, induces relaxation in coronary artery, negative inotropism and hypotensive effect in rats

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-03-28 DOI:10.1016/j.bcp.2025.116918

Raiana A. Moraes , Daniele S. Brito , Fênix A. Araujo , Rafael L.C. Jesus , Liliane B. Silva , Gabriela B. de C. Lima , Denise S. Sá , Carlos D. Silva da Silva , Laena Pernomian , Camilla F. Wenceslau , Darizy F. Silva

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引用次数: 0

Abstract

Reduced NO synthesis and/or bioavailability is related with many cardiovascular diseases, such as coronary artery disease and hypertension. This study aimed to evaluate the effects of cis-[Ru(NO)(NO2)(phen)2](PF6)2-(NONO2P) on blood pressure in normotensive and hypertensive rats. Specifically, we wanted to investigate its action on the atrial contractility, mesenteric and coronary arteries function. Male Wistar and spontaneously hypertensive rats (SHR) (13–18 weeks old) were used to assess the NONO2P effects on blood pressure and heart rate. Superior mesenteric and coronary arteries, and atria were isolated for recording to analyze force changes. Cultured endothelial cells were used to measure intracellular reactive oxygen species (ROS) generation using fluorescent dye (dihydroethidium, DHE). Acute administration of NONO2P induced hypotension in non-anesthetized normotensive and hypertensive rats. Moreover, NONO2P caused a negative inotropic effect without altering cardiac rhythmicity. Further, NONO2P displays a vasorelaxant effect on different blood vessels (mesenteric and coronary arteries). For comparison purposes, we observed that NONO2P and NTG presented with a similar potency and maximum response values in inducing relaxation in coronary arteries. On the other hand, mesenteric arteries were more sensitive to both donors, NONO2P and NTG, than the coronary artery. In addition, exposure to NONO2P induced tolerance and increased ROS levels. This is the first evidence that NONO2P induces hypotension, negative cardiac inotropism and coronary artery relaxation. In addition, pre-exposure to NONO2P induces vascular tolerance. Overall, these results may shed light on the potential therapeutic use of NONO2P, particularly in treating angina and hypertensive crises.

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.