Journal of Hypertension · Oct 26, 2026

Exercise attenuates hypertension-induced renal dysfunction alongside changes in purine metabolism and A2A and P2X7 receptor expression

By Cardoso AM, Manica A, Morsch VM et al.

BACKGROUND: Hypertension-induced renal dysfunction is associated with endothelial dysfunction and changes in purinergic signaling. Exercise training can attenuate hypertension-related disturbances in purinergic pathways, but its effects on renal purine metabolism and purinergic receptor expression remain poorly understood. We investigated these responses in L-NAME-induced hypertensive rats. METHODS: Male Wistar rats were assigned to Control, Exercise, L-NAME, and Exercise L-NAME groups (n = 10/group). Hypertension was induced by chronic Nω-nitro-L-arginine methyl ester (L-NAME) administration, and exercise consisted of 6 weeks of swimming training. Blood pressure, renal nitric oxide metabolites (NOx), renal function, serum ATP, renal ATP, ADP, and AMP hydrolysis, ADA activity, and renal expression of purinergic enzymes and P1, P2X, and P2Y receptors were evaluated. RESULTS: L-NAME increased blood pressure, serum ATP, urea, and creatinine and reduced renal NOx concentrations. Hypertensive animals showed increased CD39 and ADA expression, increased ATP hydrolysis and ADA activity, reduced A1 and A2A receptor expression, and increased P2X4 and P2X7 expression. Exercise attenuated serum ATP accumulation, changes in renal purine-metabolizing enzyme activities, and ADA expression; preserved A2A and P2X1 expression; and attenuated increases in P2X4 and P2X7 expression. Significant correlations among serum ATP, creatinine, A2A, and P2X7 expression occurred exclusively in L-NAME-treated animals. CONCLUSIONS: L-NAME-induced hypertension is associated with renal dysfunction, changes in renal purine metabolism, and selective changes in purinergic receptor gene expression. Swimming training attenuated several of these responses and improved renal function. These findings identify renal purine metabolism and A2A and P2X7 receptor expression as potential pathways associated with exercise-induced protection that warrant further mechanistic investigation.

doi.org/10.1097/hjh.0000000000004479PubMed 42937080Interventions