Antihypertensive potential of selected pyrimidine derivatives: Explanation of underlying mechanistic pathways

This study was designed to determine the effectiveness of 5-(3-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-5), 5-(4-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-8), 5-(3-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-9) and 5-(4-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-10) against hypertension. In deoxycorticosterone acetate-salt rats, SR-5, SR-8, SR-9, and SR-10 reduced blood pressure and normalized renal functions. In isolated rat aortic rings, SR-5, SR-8, SR-9, and SR-10 relaxed phenylephrine (PE) and K+-induced contractions. The vasodilator effect was endothelium-independent. Test compounds caused a rightward shift of Ca++ and PE concentration-response curves with a reduction of maximum response. SR-5, SR-8, SR-9, and SR-10 inhibited PE peak contractions in a Ca++ free medium. In guinea-pig atria, SR5, SR-8, SR-9, and SR-10 caused a mild-to-moderate inhibition of force and rate of contractions. In the aorta and heart tissues, the test compounds enhanced glutathione-s-transferase, reduced glutathione and catalase levels, improved cellular architecture, and decreased lipid peroxidation and expression of inflammatory markers: cyclooxygenase 2, tumor necrosis factor alpha, phosphorylated c-Jun N-terminal kinase, and phosphorylated-nuclear factor kappa B, evidenced in the immunohistochemistry, enzyme-linked immunosorbent assay, western blot molecular investigations and a decreased mRNA expression of calcium chann...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Source Type: research