is known to improve vasodilating mechanisms mediated by endothelium-dependent relaxing factors in the cardiac and skeletal muscle vascular beds. However, the effects of exercise training on visceral vascular reactivity, including the renal circulation, are still unclear. We used the experimental model of the isolated perfused rabbit kidney, which involves both the renal macro-and microcirculation, to test the hypothesis that exercise training improves vasodilator mechanisms in the entire renal circulation. New Zealand White rabbits were pen confined (Sed; n ϭ 24) or treadmill trained (0% grade) for 5 days/wk at a speed of 18 m/min during 60 min over a 12-wk period (ExT; n ϭ 24). Kidneys isolated from Sed and ExT rabbits were continuously perfused in a nonrecirculating system under conditions of constant flow and precontracted with norepinephrine (NE). We assessed the effects of exercise training on renal vascular reactivity using endothelial-dependent [acetylcholine (ACh) and bradykinin (BK)] and -independent [sodium nitroprusside (SNP)] vasodilators. ACh induced marked and dose-related vasodilator responses in kidneys from Sed rabbits, the reduction in perfusion pressure reaching 41 Ϯ 8% (n ϭ 6; P Ͻ 0.05). In the kidneys from ExT rabbits, vasodilation induced by ACh was significantly enhanced to 54 Ϯ 6% (n ϭ 6; P Ͻ 0.05). In contrast, BK-induced renal vasodilation was not enhanced by training [19 Ϯ 8 and 13 Ϯ 4% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n ϭ 6; P Ͼ 0.05)]. Continuous perfusion of isolated kidneys from ExT animals with N -nitro-L-arginine methyl ester (L-NAME; 300 M), an inhibitor of nitric oxide (NO) biosynthesis, completely blunted the additional vasodilation elicited by ACh [reduction in perfusion pressure of 54 Ϯ 6 and 38 Ϯ 5% for ExT and L-NAME ϩ ExT, respectively (n ϭ 6; P Ͻ 0.05)]. On the other hand, L-NAME infusion did not affect ACh-induced vasodilation in Sed animals. Exercise training also increased renal vasodilation induced by SNP [36 Ϯ 7 and 45 Ϯ 10% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n ϭ 6; P Ͻ 0.05)]. It is concluded that exercise training alters the rabbit kidney vascular reactivity, enhancing endothelium-dependent and -independent renal vasodilation. This effect seems to be related not only to an increased bioavailability of NO but also to the enhanced responsiveness of the renal vascular smooth muscle to NO. chronic exercise; endothelial dysfunction; isolated perfused rabbit kidney IT IS WELL KNOWN THAT THE endothelium plays a role of paramount importance in the regulation of the vasomotor tone (for review, see Ref. 26). The endothelial cells synthesize and release several relaxing and contracting diffusible substances that interact with the underlying vascular smooth muscle, thus contributing to the continuous modulation of vascular reactivity (26). The best-characterized endothelium-derived relaxing factors are nitric oxide (NO) and prostacyclin (PGI 2 ), which can be released by physical (shear stress by the fl...

It has been shown previously that high glucose causes direct and acute endothelial dysfunction in non-diabetic isolated rabbit kidney. This study assessed whether exercise training is able to maintain normal renal vascular endothelial function despite high glucose exposure. Animals were pen confined (SED) or treadmill trained over a 12-week period (ExT). Kidneys isolated from SED and ExT rabbits were continuously perfused ex vivo during 3 h with Krebs-Henseleit solutions containing normal (5.5 mm) or high (15 mm) concentrations of d-glucose. In the SED 5.5 group, acetylcholine (ACh) induced dose-related vasodilator responses, reaching the maximum of 41+/- 2% (n=10; P<0.05). In the kidneys perfused with high concentrations of glucose (SED 15), endothelium-dependent vasodilation was significantly blunted. Maximal relaxation in the presence of 15 mm glucose was of 19 +/- 2%, which was significantly different from the SED 5.5 group (41+/- 2%, n=10, P<0.01). In the ExT 5.5 group, ACh-induced vasodilation was significantly enhanced when compared with the SED 5.5 group, reaching the maximum of (52+/- 2%, n=10, P<0.05). Moreover, the exposure of the renal circulation of ExT animals to high glucose did not change endothelium-dependent vasodilation induced by ACh (46+/- 3%, n=6), when compared with the ExT 5.5 group. Finally, exercise training prevented the deleterious effects of high glucose on endothelial-dependent renal vasodilation (SED 15: 19+/- 2% vs. ExT 15: 46+/- 3%; P<0.05). It is concluded that exercise training protects the rabbit renal circulation against endothelial dysfunction elicited by acute exposure to moderately elevated glucose levels, corresponding to the postprandial glycemia of diabetes type 2 patients under treatment. The enhanced renal vasodilator reserve elicited by exercise training turns out to be a response that protects the kidney from the deleterious effects of glycemic peaks.