Abstract 373: Impacts of Apocynin and Allopurinol on Exercise Training-increased Nitric Oxide Synthase Activity and Expression in the Kidney of SHR and WKY
It has been recently reported that the exercise training (Ex) increases nitric oxide (NO) production and NO synthase (NOS) expression not only in vasculatures but also in the kidney of spontaneously hypertensive rats (SHR) with the reduction of systemic blood pressure. To clarify the mechanism of the Ex-increased NOS expression, the impacts of inhibitors of NADPH oxidase and xanthine oxidase on the Ex-increased NOS activity and expression were examined in SHRs and Wistar-Kyoto rats (WKY). Five week-old, male SHR or WKY were trained with treadmill running. Apocynin (2 mmol/L in drinking water), an inhibitor of NADPH oxidase or allopurinol (1.5 mmol/L in drinking water), an inhibitor of xanthine oxidase was given for drug treatments. After 8 weeks, H2O2 and NO2/NO3 (NOx) in plasma and urine were measured. The NOS activity and expression were examined in the kidney cortex, the outer medulla, the inner medulla and thoracic aorta. In both SHR and WKY, the Ex significantly increased H2O2 and NOx in plasma and urine, NOS activity and endothelial and neuronal NOS (eNOS and nNOS) expressions in the kidney cortex, the outer medulla, the inner medulla and thoracic aorta (p<0.01 in each). Apocynin significantly decreased basal levels of H2O2 and NOx in plasma and urine, NOS activity and eNOS and nNOS expressions (p<0.01 in each) in the kidney sections and aorta of SHR, but did not affect all parameters in those of WKY. Apocynin blocked the Ex-induced changes of H2O2 and NOx levels and renal and aortic NOS activity and expression in WKY and aortic NOS activity and expression in SHR, but it did not block the Ex-induced changes of H2O2 and NOx levels or renal NOS activity and expression in SHR. In contrast to apocynin, allopurinol did not affect basal levels of all these parameters in SHR or WKY. Allopurinol blocked the Ex-induced changes of H2O2 and NOx levels and renal NOS expression in SHR but did not block the Ex- induced changes of aortic NOS expression in SHR or all parameters in WKY. These results indicate that the Ex-increased NOS activity and expression in aorta were mediated through NADPH oxidase in both SHR and WKY. The Ex-induced NOS activity and expression in the kidney were mediated through NADPH oxidase in WKY but through xanthine oxidase in SHR.
- © 2012 by American Heart Association, Inc.