Effect of a High Salt Diet on Microvascular Antioxidant Enzymes

Abstract

High dietary salt intake decreases the endothelium-dependent dilation of skeletal muscle arterioles by inhibiting local nitric oxide (NO) activity without changing vascular smooth muscle responsiveness to NO. Under these conditions, microvascular walls show evidence of oxidative stress, and scavengers of reactive oxygen species (ROS) abolish this oxidative stress and restore normal arteriolar responses to acetylcholine (ACh). We tested the hypothesis that the salt-dependent appearance of microvascular ROS, and accompanying reduction in endothelium-dependent dilation, is due to a decrease in antioxidant enzyme expression or activity. We studied spinotrapezius muscle microvessels in rats fed normal (NS) (0.45%) or high (HS) (7%) salt diets for 4–5 weeks. Western analysis of arteriolar and venular protein showed no difference between groups in the content of superoxide dismutase (Cu/Zn SOD), catalase, or glutathione peroxidase. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) increased arteriolar and venular oxidant activity (assessed by tetranitroblue tetrazolium reduction) by the same amount in both groups, suggesting similar levels of catalase activity. 3AT did not affect arteriolar responses to ACh in either group. The Cu/Zn SOD inhibitor diethyldithiocarbamate increased arteriolar and venular oxidant activity to a lesser extent in HS rats, suggesting reduced Cu/Zn SOD activity in this group. Cu/Zn SOD inhibition decreased arteriolar responses to ACh only in NS rats. These findings suggest that endogenous Cu/Zn SOD preserves the endothelium-dependent control of arteriolar tone in NS rats, and that a reduction in Cu/Zn SOD activity contributes to the loss of arteriolar NO activity in HS rats.

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca2+ signaling and NO production in rat aorta

“…This hypothesis is supported by the report of Fukai et al (6), who demonstrated that ANG II increases extracellular SOD expression in mouse aorta, both in vivo and in organoid culture. Additional support for this hypothesis is provided by the findings of other investigators, who reported that a reduction in extracellular SOD activity contributes to elevated superoxide levels and impaired flow-induced dilation in patients with chronic heart failure (13) and that reduced Cu/Zn SOD activity contributes to elevated superoxide levels and loss of arteriolar NO activity in rats on a HS diet (14). The hypothesis that oxidative stress is lower and NO-dependent relaxation is preserved to a greater extent in aortas from ANG II-infused rats fed a HS diet is supported by the results of our functional studies showing that Tempol causes less relaxation and L-NAME causes a larger contraction in aortas from ANG II-infused animals on a HS diet compared with vessels from rats on a HS diet without ANG II infusion (Fig.…”

Reduced Angiotensin II and Oxidative Stress Contribute to Impaired Vasodilation in Dahl Salt-Sensitive Rats on Low-Salt Diet

“…In contrast to findings demonstrating that large elevations in Ang II levels induce hypertension and increase oxidative stress, 15,17,24 Fukai et al 26 recently reported that Ang II increases extracellular superoxide dismutase (ecSOD) activity, ecSOD mRNA, and ecSOD protein expression in mouse aorta and increases ecSOD mRNA in human aortic vascular smooth muscle cells. Other studies indicate that reduced Cu/Zn SOD activity contributes to impaired ACh-induced dilation in arterioles of normotensive rats on HS diet 10 and that Cu/Zn SOD and Mn SOD expression are reduced in the kidney of SS rats fed HS diet. 16 Overall, those findings suggest that exposure to chronically low Ang II levels during HS diet (or in SS rats on LS diet) could lead to increased oxidative stress because of downregulation of antioxidant enzymes such as superoxide dismutase.…”

Protective Effect of Dietary Potassium Against Vascular Injury in Salt-Sensitive Hypertension

“…15 Although arterial NADPH oxidase activity was suppressed in potassium-supplemented and salt-loaded DS rats compared with normal-salt diet-fed animals in this study, ROS generation from cuffed arteries was similar in these animals. Thus, NADPH oxidase-independent ROS-producing or -scavenging systems, eg, mitochondrial ROS generation 30 and microvascular superoxide dismutase, 31 which have been reported to be stimulated by salt loading but might not be inhibited by dietary potassium, may also contribute to ROS production in cuffed arteries of salt-loaded DS rats.…”