Celastrol ameliorates energy metabolism dysfunction of hypertensive rats by dilating vessels to improve hemodynamics

Abstract

The impact of hypertension on tissue and organ damage is mediated through its influence on the structure and function of blood vessels. This study aimed to examine the potential of celastrol, a bioactive compound derived from Tripterygium wilfordii Hook F, in mitigating hypertension-induced energy metabolism disorder and enhancing blood perfusion and vasodilation. In order to investigate this phenomenon, we conducted in vivo experiments on renovascular hypertensive rats, employing indirect calorimetry to measure energy metabolism and laser speckle contrast imaging to evaluate hemodynamics. In vitro, we assessed the vasodilatory effects of celastrol on the basilar artery and superior mesenteric artery of rats using the Multi Wires Myograph System. Furthermore, we conducted preliminary investigations to elucidate the underlying mechanism. Moreover, administration of celastrol at doses of 1 and 2 mg/kg yielded a notable enhancement in blood flow ranging from 6 to 31% across different cerebral and mesenteric vessels in hypertensive rats. Furthermore, celastrol demonstrated a concentration-dependent (1 × 10^–7 to 1 × 10^–5 M) arterial dilation, independent of endothelial function. This vasodilatory effect could potentially be attributed to the inhibition of Ca²⁺ channels on vascular smooth muscle cells induced by celastrol. These findings imply that celastrol has the potential to ameliorate hemodynamics through vasodilation, thereby alleviating energy metabolism dysfunctions in hypertensive rats. Consequently, celastrol may hold promise as a novel therapeutic agent for the treatment of hypertension.