Oxidative Stress and Renal Dysfunction in Salt-Sensitive Hypertension

Abstract

Hypertension is a risk factor for the development of end-stage renal disease. The mechanisms underlying hypertensive nephropathy are poorly understood. There is evidence, however, that in hypertension there is an accumulation of partially reduced oxygen and its derivatives, known collectively as reactive oxygen species, which may contribute to progressive renal dysfunction. In the present study, we assess the contribution of oxidative stress in the development of salt-dependent hypertensive nephrosclerosis. Going beyond previous end point studies, which inferred renal function either indirectly or only qualitatively, we have determined oxidative stress concurrently with direct and quantitative measurements of renal function (via inulin and p-aminohippuric acid clearances). Moreover, in this time-dependent study, the measurements have been taken under low- as well as high-salt diets. As was expected from previous studies, in the Dahl salt-sensitive rat, a high-salt diet (8% NaCl) resulted in the development of hypertension, in a decreased glomerular filtration rate, and in a decreased renal plasma flow as compared with the normotensive control, the Dahl salt-resistant rat. In addition, however, we found clear evidence for the accumulation of reactive oxygen species in renal tissue homogenates of Dahl salt-sensitive rats on the high-salt diet. Our time-dependent protocol also indicated that renal oxidative stress follows, in time, the development of hypertension. We also found that after 2 weeks of increased salt loading, Dahl salt-sensitive rats excreted less cyclic guanosine monophosphate and NO_x than Dahl salt-resistant rats on the same diet. It is known that urinary cyclic guanosine monophosphate and NO_x represent the activity and stable derivatives of renal NO·, respectively, and that they closely correlate with renal vascular resistance. Therefore, our results suggest that, in the Dahl salt-sensitive rat, increased oxidative stress is associated with salt-dependent hypertensive nephrosclerosis and that decreased NO· bioavailability may represent a common factor responsible for the vascular and glomerular dysfunction.

Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension

“…OX accompanying hypertension in animal models includes spontaneous hypertension, 22 renovascular hypertension, 23 deoxycorticosterone acetate-salt hypertension model 24 and obesity-related hypertension. 25 Moreover, reducing superoxide radicals by infusion of SOD significantly decreases BP in spontaneously hypertensive rats.…”

Effects of Black Race on Forearm Resistance Vessel Function

“…Another possibility to consider is the known increased incidence of salt-sensitive hypertension in black Americans, 28 because this condition is also associated with impaired vascular function in human subjects, 29 evidence of decreased nitric oxide production, 30 and increased oxidative stress in experimental models. 31 It is also possible that the results are attributable to different distributions of genetic variants of adrenergic receptors 4 or eNOS. 32 Further investigation of these and other potential mechanisms was beyond the scope of the present study.…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…Previous studies by Landmesser et al 2002; and Loscalzo et al (Welch et al 1997;Maytin et al 1999;Forgione et al 2000;Trolliet et al 2001;Nedeljkovic et al 2003;Weiss et al 2003) demonstrate that oxidative stress is an important molecular component of vascular disease, including hypertension and atherosclerosis. Increased understanding of the enzymatic and molecular development of cardiovascular disease may allow for more effective treatment and earlier intervention.…”