Effect of Nicorandil on Endothelial Markers and Tissue Remodeling in Pulmonary Arterial Hypertension Model of Male Rats

Taha Hashim Ahmed; Bahir Abdul-Razzaq Mshimesh; Israa Burhan Raoof

doi:10.54133/ajms.v5i1S.334

Authors

Taha Hashim Ahmed Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq https://orcid.org/0009-0006-4298-9015
Bahir Abdul-Razzaq Mshimesh Department of Pharmacology and Toxicology, College of Pharmacy, Mutansiriya University, Baghdad Iraq
Israa Burhan Raoof Department of Clinical Lab Sciences, College of Pharmacy, Mustansiriya University, Baghdad, Iraq

DOI:

https://doi.org/10.54133/ajms.v5i1S.334

Keywords:

Anti-apoptotic effect, Endothelin-1, Nicorandil,, NFκB, Nitric oxide, Pulmonary arterial hypertension

Abstract

Background: Chronic pulmonary arterial hypertension (PAH) is a rare, long-lasting illness that makes pulmonary artery endothelial cells (PAEC) not work properly and leads to heart failure and death. Objective: To evaluate the effect of nicorandil in the treatment of PAH compared to tadalafil in a rat model of monocrotaline-induced PAH. Methods: Monocrotaline injection (60 mg/kg) was used for the induction of PAH in male rats; healthy control and induction groups were not treated. The other 4 groups were treated with either nicorandil or tadalafil with or without treatment blockers (glimepiride and N-Nitroarginine methyl ester (L-NAME)) for 21 days orally. Serum was obtained for assessment of endothelin-1 (ET-1) and tissue harvested for nuclear factor kappa B (NFκB) by ELISA, western blot analysis of endothelial nitric oxide synthase (eNOS), and an apoptosis assay to examine the endothelial function. Results: Nicorandil showed a significant reduction in ET-1 and significant elevation in eNOS compared to the induction group, with comparable efficacy to tadalafil; blocker groups showed significantly elevated levels of ET-1 and reduced levels of eNOS compared to healthy control; NFκB was significantly inhibited in nicorandil and tadalafil groups and significantly elevated in blocker and induction groups; while in the TUNEL apoptosis assay, nicorandil showed the highest level of inhibition to apoptosis with apparently normal endothelium lining. Conclusions: Nicorandil shows anti-inflammatory, antiapoptotic, and enhanced endothelial morphology and function compared to the induction model.

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