leaf extract induces vasorelaxation via endothelium-dependent hyperpolarization and calcium channel blockade in mesenteric arterial beds isolated from L-NAME hypertensive rats.
Clin Exp Hypertens. 2020 Jan 22:1-12. Epub 2020 Jan 22. PMID: 31965874
: An aqueous extract ofleaves (MOE) is known to cause relaxation of mesenteric resistance arteries of rats in which hypertension has been induced by the administration of L-NAME, but the mechanism(s) of action of MOE remains unclear. The purpose of this study was to investigate these mechanisms in mesenteric arterial beds isolated from L-NAME induced hypertensive rats. Methods: An investigation of vascular reactivity was conducted on isolated mesenteric arterial beds by measuring the changes in perfusion pressure using ansystem.: MOE (0.001-3 mg in 0.1 ml injection volume) caused a dose-dependent relaxation in methoxamine (5µM) pre-contracted arterial beds, which was partially abolished by endothelium removal. The endothelium-dependent component of vasorelaxation was insensitive to both L-NAME (100 µM) and indomethacin (10 µM), while completely inhibited in high KCl (45 mM)-induced contraction. MOE (1 and 3 mg/ml) showed a dose-dependent inhibitory effect on CaCl-induced contractions of denuded preparations in Ca-free medium containing a high KCl (60 mM) or methoxamine (10µM). In Ca-free medium, MOE (3 mg/ml) also inhibited phenylephrine-induced contractions of denuded preparations. Conclusion: These findings suggest that MOE relaxes mesenteric arterial beds of L-NAME hypertensive rats via both endothelium-dependent and endothelium-independent mechanisms. The endothelium-dependent action occurred via endothelium-derived hyperpolarizing factor-mediated hyperpolarization. The endothelium-independent action was related to blocking the entry of extracellular Cavia voltage-operated and receptor-operated Cachannels, and inhibiting mobilization of sarcolemmal Cavia inositol trisphosphate receptor Cachannels. MOE may be potentially useful as a natural vasodilator against hypertension.