Resistance arteries significantly contribute to peripheral vascular resistance, and also determine insulin-sensitivity by controlling blood flow to skeletal muscle. Increased microvascular tone therefore facilitates the development of hypertension and insulin-resistance. Surrounding most blood vessels, perivascular adipose tissue (PVAT) exerts a vasorelaxant ‘anti-contractile’ effect. Few studies on skeletal muscle resistance arteries have investigated this vasorelaxant effect and the role of insulin. We aimed to address this through establishing a novel in vitro model.Design and Method:
Vascular contractility of arterial segments, with (+) or without (-) PVAT, from hindlimb skeletal muscle resistance arteries of healthy male Wistar rats was assessed by wire myography. Viable vessels achieved tensions > = 0.3mN/mm when challenged with 60mM high-K+ physiological saline solution (KPSS). Arterial segments were subsequently pre-constricted with noradrenaline (30 μM) and endothelial function was confirmed by vasodilation (> = 25% reduction of noradrenaline-induced tension) in response to carbachol (30 μM, ∼10min). Vessels were challenged with either serotonin or noradrenaline (−8 to −4.5 log10M). The effects of insulin (2nM, 30 min pre-incubation) were investigated on the noradrenaline-induced dose-response. Responses were normalised to post-dose-response KPSS-induced constrictions. Statistical analyses were performed via two-way ANOVA with Bonferroni post-hoc analysis.Results:
PVAT exerted an endothelium-independent anti-contractile effect in response to serotonin (-PVAT: n = 8; +PVAT: n = 8; P < 0.0001), which was potentiated by endothelium (-Endothelium: n = 8; +Endothelium: n = 3; P < 0.0001). Contrastingly, endothelium but not PVAT exerted anti-contractility in response to noradrenaline (-Endothelium n = 8, +Endothelium n = 10, P < 0.0001). Following insulin pre-incubation, noradrenaline induced either PVAT-mediated anti-contractility or pro-contractility depending upon the absence (Noradrenaline: n = 8; Insulin: n = 4; P = 0.009) or presence (Noradrenaline: n = 10; Insulin: n = 2; P = 0.0007) of endothelium.Conclusions:
Serotonergic and adrenergic stimulation elicit anti-contractile responses through PVAT and the endothelium, respectively. Consistent with previous studies, insulin acts as both a vasodilator and vasoconstrictor. This model should allow for obesity-associated microvascular dysfunction, in which PVAT and endothelial function are impaired, to be characterised in skeletal muscle resistance arteries.