The aim of this study was to investigate whether the effects of aging on oxidative stress markers and expression of major oxidant and antioxidant enzymes associate with impairment of renal function and increases in blood pressure. To explore this, we determined age‐associated changes in lipid peroxidation (urinary malondialdehyde), plasma and urinary hydrogen peroxide (H₂O₂) levels, as well as renal H₂O₂ production, and the expression of oxidant and antioxidant enzymes in young (13 weeks) and old (52 weeks) male Wistar Kyoto (WKY) rats. Urinary lipid peroxidation levels and H₂O₂ production by the renal cortex and medulla of old rats were higher than their young counterparts. This was accompanied by overexpression of NADPH oxidase components Nox4 and p22^phox in the renal cortex of old rats. Similarly, expression of superoxide dismutase (SOD) isoforms 2 and 3 and catalase were increased in the renal cortex from old rats. Renal function parameters (creatinine clearance and fractional excretion of sodium), diastolic blood pressure and heart rate were not affected by aging, although slight increases in systolic blood pressure were observed during this 52‐week period. It is concluded that overexpression of renal Nox4 and p22^phox and the increases in renal H₂O₂ levels in aged WKY does not associate with renal functional impairment or marked increases in blood pressure. It is hypothesized that lack of oxidative stress‐associated effects in aged WKY rats may result from increases in antioxidant defenses that counteract the damaging effects of H₂O₂.

Background and purpose: This study evaluated the signalling coupled to the α₁‐adrenoceptor‐induced stimulation of the Cl⁻/HCO₃⁻exchanger in hypertension.Experimental approach: The Na⁺‐independent HCO₃⁻transport system activity was assayed as the initial rate of pH_irecovery after an alkaline load (CO₂/HCO₃removal) in immortalized renal proximal tubular epithelial cells from spontaneously hypertensive rat (SHR) and their normotensive control (Wistar Kyoto rat; WKY).Key results: Noradrenaline increased Cl⁻/HCO₃⁻exchanger activity with EC₅₀values of 0.6 and 5.3 μMin SHR and WKY cells, respectively. These effects were abolished by prazosin, but not by yohimbine. Phenylephrine increased Cl⁻/HCO₃⁻exchanger activity in SHR and WKY cells (EC₅₀of 2.6 and 4.9 μM, respectively). Phenylephrine‐mediated increase in Cl⁻/HCO₃⁻exchanger activity in WKY and SHR cells was inhibited by protein kinase C (PKC), MAPK/ERK kinase (MEK) and p38 mitogen‐activated protein kinase (p38 MAPK) inhibitors. The expression of α_1A‐ and α_1B‐adrenoceptors was identical in WKY and SHR cells. SHR cells generated more H₂O₂than WKY cells. In SHR cells, the NADPH oxidase inhibitor apocynin reduced their increased ability to generate H₂O₂and abolished their hypersensitivity to phenylephrine, but failed to affect basal Cl⁻/HCO₃⁻exchanger activity. H₂O₂‐dependent stimulation of Cl⁻/HCO₃⁻exchange activity was significantly higher in SHR than in WKY cells.Conclusions and implications: Differences between WKY and SHR cells on their sensitivity to α₁‐adrenoceptor stimulation did not correlate with the abundance of α_1A‐ and α_1B‐adrenoceptors and may be related to the increased generation of H₂O₂, which may amplify the response downstream of α₁‐adrenoceptor activation.British Journal of Pharmacology(2008)153, 1445–1455; doi:10.1038/bjp.2008.16; published online 25 February 2008