Redox regulation of the afferent arteriole and tubuloglomerular feedback

Oxidative stress implies an increased production of reactive oxygen species (ROS) or a decreased capacity to metabolize them. Superoxide anion (O-2(.-)) can bioinactivate nitric oxide (NO). Therefore, many effects of ROS are manifest as NO deficiency. The afferent arteriole and macula densa cell both contain a full complement of components of nicotine adenine dinucleotide phosphate (NADPH) oxidase that generates O-2(.-). Nitric oxide synthase (NOS) type 1 or neuronal NOS (nNOS) is expressed in the macula densa and NOS type II or endothelial NOS (eNOS) in the afferent arteriole. Whole animal studies in models of hypertension and oxidative stress demonstrate that metabolism of O-2(.-) by a superoxide dismutase (SOD) mimetic can reduce renal vascular resistance. In vivo studies of single nephron function and in vitro studies with the double-perfused juxtaglomerular apparatus preparation have shown extensive interaction between O-2(.-) and NO in macula densa to regulate afferent arteriolar tone mediated by the tubuloglomerular feedback response. In vitro studies of rabbits isolated, perfused afferent arterioles have shown a similar interaction in this vessel. These data indicate important roles for O-2(.-) in the macula densa and afferent arterioles to enhance preglomerular resistance in animal models of oxidative stress. As an increase in afferent arteriolar resistance can precede hypertension, oxidative stress could be important in determining the long-term blood pressure and thereby contribute to hypertension.