Adaptation of coronary microvascular exchange in arterioles and venules to exercise training and a role for sex in determining permeability responses

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Abstract
Studies of physical performance and energy metabolism during and following exercise have shown significant sex-specific musculoskeletal adaptations; less is known of vascular adaptations, particularly with respect to exchange capacity. In response to adenosine (ADO), a metabolite produced during exercise, permeability ( Ps) of coronary arterioles from female pigs changed acutely; the magnitude and direction of the change (Δ Ps) were determined by training status. In the present study Psto albumin was assessed in arterioles ( n = 138) and venules ( n = 24) isolated from hearts of male ( N = 2 7) and female ( N = 59) pigs in the exercise training group (EX). We evaluated the hypothesis that coronary microvessel exchange adapts to endurance exercise training not by altering basal Ps, per se, but by elevating Pson exposure to ADO. In contrast, training resulted in a reduction of basal Psin all arterioles, and in venules from males, with no change in venules from EX females. Exposure to ADO resulted in the predicted increase in Psexcept for venules from EX males where Pswas reduced. Δ Psresponses of arterioles to mediators of adenylyl cyclase (isoproterenol)- and guanylyl cyclase (atrial natriuretic peptide)-signaling pathways were attenuated in EX pigs relative to pigs in the sedentary group. The adaptation of EX arterioles involves an upregulation of a nitric oxide-dependent pathway since nitric oxide synthase inhibition blocks Δ Psby ADO. Thus adaptation of microvascular exchange capacity to endurance exercise training not only occurs but also involves multiple mechanisms that differ in arterioles and venules with their relative contribution to net flux being a function of sex.