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 (P_s) of coronary arterioles from female pigs changed acutely; the magnitude and direction of the change (P_s) were determined by training status. In the present study P_s to albumin was assessed in arterioles (n=138) and venules (n=24) isolated from hearts of male (N=27) and female (N=59) EX pigs. We evaluated the hypothesis that coronary microvessel exchange adapts to endurance exercise training (EX) not by altering basal P_s, per se, but by elevating P_s on exposure to ADO. In contrast, training resulted in a reduction of basal P_s in all arterioles, and in venules from males, with no change in venules from EX females. Exposure to ADO resulted in the predicted increase in P_s except for venules from EX males where P_s was reduced. P_s responses of arterioles to mediators of adenylyl cyclase- (isoproterenol) and guanylyl cyclase- (atrial natriuretic peptide) signaling pathways were attenuated in EX relative to SED pigs. The adaptation of EX arterioles involves up-regulation of an NO-dependent pathway as nitric oxide synthase inhibition blocks P_s by ADO. Thus, adaptation of microvascular exchange capacity to endurance exercise training not only occurs but involves multiple mechanisms that differ in arterioles and venules with their relative contribution to net flux being a function of sex.