Vasorelaxant and Antihypertensive Effects of Neferine in Rats: An In Vitro and In Vivo Study

Abstract

The present study was performed to examine the antihypertensive effect of neferine in hypertensive rats and its relaxant mechanisms in isolated rat thoracic aorta. The antihypertensive effect was evaluated by tail-cuff methods on N^G-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg BW) 4-week hypertensive-induced hypertensive rats. The vasorelaxant effect and its mechanisms were studied by the organ bath technique in the thoracic aorta isolated from normotensive rats. The results indicated that the treatment of neferine (1 mg/kg and 10 mg/kg) markedly decreased the systolic blood pressure (SBP) when compared with the hypertension group (137.75 ± 10.14 mmHg and 132.23 ± 9.5 mmHg, respectively, p < 0.001), without affecting the heart rate. Moreover, neferine (10⁻¹² − 10⁻⁴ M) exhibited concentration-dependent vasorelaxation in endothelium-intact rings (E_max values = 98.95 ± 0.66% and pD₂ = 7.93 ± 0.28) and endothelium-denuded rings (E_max values = 90.61 ± 1.91% and pD₂ = 6.85 ± 0.36). The effects of neferine were reduced by pre-incubation with L-NAME and 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) but not with pre-incubation with indomethacin and K⁺channel blockers. Neferine attenuated the contractions induced by phenylephrine and caffeine in a Ca²⁺-free solution and also inhibited in CaCl₂- and phenylephrine-induced contracted rings. Our study suggests that neferine exhibited hypertensive potential, induced vasorelaxation through the endothelium nitric oxide synthase (eNOS)/nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway and involved the modulation of Ca²⁺ influx through Ca²⁺ channels and intracellular Ca²⁺ release from the sarcoplasmic reticulum.

Key words

endothelium-dependent - endothelium-independent - hypertension - neferine - nelumbonaceae - Nelumbo nucifera - rat aorta vasorelaxation

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