Oxidative imbalance and kidney damage in spontaneously hypertensive rats: activation of extrinsic apoptotic pathways.

In both humans and animals, essential hypertension acts as a risk factor for subclinical kidney damage and precedes renal dysfunction. Several lines of evidence indicate that hypertension and oxidative stress are closely related. The increase in vascular oxidative stress plays a key role in the pathophysiological consequences of hypertension, including kidney disease. Our study examined this issue in spontaneously hypertensive rat (SHR), a reliable model of essential hypertension. We used SHR 20 weeks old when hypertension is stably developed, vascular remodeling started, but kidney function is preserved. We examined plasmatic pro-oxidant and antioxidant status showing a significant alteration in oxidative balance in SHR. As index of oxidative damage, we evaluated lipid peroxidation in kidney, liver, and skeletal muscle, detecting a significant rise in lipid peroxidation levels in all SHR tissues, particularly relevant in kidney. In addition, we analyzed the expression of cytoplasmic antioxidant enzymes, superoxide dismutase 1 (SOD1) and glutatione S-tranferasi P1 (GSTP1). In SHR liver, SOD1 expression slight increased while we have not detected any variation in other tissues. Concerning GSTP1, SHR renal tissues did not display variations in enzyme expression, while in the other tissues, we observed a significant increase in both monomeric and pro-apoptotic dimeric form of the enzyme. By analyzing apoptotic signal, we founded c-Jun N-terminal kinase (JNK) activation in all SHR tissues, but only kidney presented extrinsic apoptotic pathway activation. Our results suggest that, in hypertensive animals with preserved renal function, despite the remarkable oxidative damage of renal tissues, only the extrinsic apoptotic pathway is activated.