Andrographolide Protects Against Lipopolysaccharide-Induced Vascular Hyporeactivity by Suppressing the Expression of Inducible Nitric Oxide in Periaortic Adipose

Abstract

This study investigated the role of perivascular adipose tissue (PVAT) in the beneficial effects of andrographolide on vascular reactivity in endotoxaemic rats. After being challenged by lipopolysaccharide (4 mg/kg intraperitoneally), the rats were treated with andrographolide (1 mg/kg intraperitoneally). The response to phenylephrine of aortic rings with or without PVAT was recorded. Vascular relaxing effect of PVAT was determined by bioassay experiments. Inducible nitric oxide synthase (iNOS) in aortic PVAT was tested by Western blot, immunofluorescence, and quantitative polymerase chain reaction. Lipopolysaccharide injection lowered the contraction force induced by phenylephrine in aortic rings with or without PVAT and andrographolide treatment reversed these effects. In bioassay experiments, transferring bathing solution incubated with a PVAT+ ring to a PVAT- ring induced relaxation in the recipient. This relaxing effect of PVAT from endotoxaemic rats was more potent than the rats treated with vehicles. Andrographolide treatment decreased the relaxing effect of PVAT in endotoxaemic rats. The levels of iNOS protein and messenger RNA in PVAT were significantly higher in endotoxaemic rats than in the rats treated with vehicles. Andrographolide treatment decreased PVAT iNOS protein and messenger RNA levels in endotoxaemic rats. Our results suggest that andrographolide restores vascular reactivity in endotoxaemic rats by downregulation of iNOS in PVAT.

Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway

“…Western blot analysis was performed as previously described [ 17 ]. Briefly, the cardiomyocytes samples were lysed in lysis buffer on ice for 20 min.…”

The role of perivascular adipose tissue in vasoconstriction, arterial stiffness, and aneurysm

“…Transferring bathing solution incubated with PVAT from endotoxemic rats potentiated PVAT-induced relaxation in the recipient vessel rings. The mechanisms are unclear, but the levels of inducible NO synthase (iNOS) protein and mRNA in endotoxemic PVAT were significantly higher than those in the control PVAT [51]. Additionally, inflammation and oxidative stress in obese PVAT might modulate endothelial function.…”

Sepse experimental aumenta a ação anti-contrátil do tecido adiposo perivascular em aortas de ratos

“…Em conjunto, os dados apresentados mostram que o PVAT produz vários elementos vasoativos que participam da regulação e manutenção do tônus vascular (Lu et al, 2010;Rajsheker et al, 2010;Szasz & Webb, 2012;Lee et al, 2014;Ayala-Lopez et al, 2014). A expressão da enzima iNOS também foi descrita em PVAT de aortas em condição de endotoxemia (Hai-Mei et al, 2013). Além disso, em situações não fisiológicas, o PVAT produz citocinas pró-inflamatórias, O 2 e H 2 O 2 (Gao et al, 2006;Du et al, 2015;).…”