Influence of exercise and perivascular adipose tissue on coronary artery vasomotor function in a familial hypercholesterolemic porcine atherosclerosis model

Abstract

Our lab has shown that left circumflex coronary artery (LCX) perivascular adipose tissue (PAT) blunts endothelin-1 (ET-1)-induced maximal contractions in normal pigs on low- and high-fat diets. Other studies report that PAT exerts anticontractile effects on agonist-induced arterial contraction via release of a relaxing factor that acts on the underlying vasculature. The purpose of this study was to test the hypotheses that PAT blunts LCX contraction in familial hypercholesterolemic pigs and that exercise training (Ex) augments this anticontractile effect. Male familial hypercholesterolemic pigs were divided into Ex (n = 13) and sedentary (Sed) (n = 15) groups. LCX reactivity to angiotensin II (ANG II), bradykinin (BK), ET-1, and sodium nitroprusside (SNP) was evaluated in vitro with intact or removed PAT in Sed and Ex familial hypercholesterolemic pigs. LCX relaxation induced by BK and SNP was not altered by Ex or PAT removal. LCX contractions stimulated by ANG II and ET-1 were not significantly altered by Ex or PAT removal across doses; however, Ex did act to significantly reduce ET-1 maximal contractions in familial hypercholesterolemic pig LCX compared with Sed familial hypercholesterolemic pig LCX, independent of PAT (P < 0.05). We conclude that LCX PAT in Sed and Ex familial hypercholesterolemic pigs exerts no substantial anticontractile influence over LCX vasomotor responses to endogenous constrictors such as ANG II and ET-1. Our results suggest that exercise training significantly reduces familial hypercholesterolemic pig LCX maximal contractile responses to the endogenous constrictor ET-1, independent of PAT.

Lean and Obese Coronary Perivascular Adipose Tissue Impairs Vasodilation via Differential Inhibition of Vascular Smooth Muscle K + Channels

“…5-7;12 Other studies in lean or hypercholesterolemic swine show little/no anti-contractile effect of coronary PVAT in response to endothelin-1, angiotensin II, or the thromboxane A2 mimetic U46619. 6;39;40 Results from the present study further support the distinct vascular effects of coronary PVAT in that lean and obese coronary PVAT significantly attenuate coronary vasodilator responses to adenosine. This impaired dilator response is directly related to effects of PVAT-derived factors on smooth muscle K + channels, as adenosine-induced dilation was unaffected by endothelial denudation and was essentially abolished by pre-constriction with KCl ( Figure 2A and 2B ).…”

Perivascular Adipose Tissue in Vascular Function and Disease

“…In support of this, there is accumulating evidence that PVAT has vasodilator effects (also termed anti-contractile effects) in various vascular beds, and this function has been shown to be impaired in hypertension 35–38 and metabolic syndrome. 35, 39–43 Substantial evidence exists that adipose-derived factors, such as leptin, resistin, and TNF-α, secreted under conditions of inflammation, can attenuate vasodilatation, 44–50 and such factors may be produced by PVAT. Indeed, a recent study demonstrated the importance of inflammation in PVAT-mediated regulation of vascular tone.…”

Human perivascular adipose tissue dysfunction as a cause of vascular disease: Focus on vascular tone and wall remodeling

“…Subsequently, it was confirmed that PVAT reduces vascular reactivity in response to not only norepinephrine but also serotonin, phenylephrine and angiotensin II (Lohn et al, 2002). This vasorelaxant effect of PVAT is mostly observed in animal tissues such as mesenteric arteries of rats/mice (Galvez et al, 2006;Takemori et al, 2007), venous rings of rats (Lu et al, 2011) and coronary arteries of pigs (Bunker and Laughlin, 2010).…”