Time‐Course and Mechanisms of Restored Vascular Relaxation by Reduced Salt Intake and Angiotensin II Infusion in Rats Fed a High‐Salt Diet

Abstract

Objective: This study determined the mechanisms and time-course of recovery of vascular relaxation in middle cerebral arteries (MCA) of salt-fed Sprague-Dawley rats returned to low salt (LS) diet (0.4% NaCl) or infused with low-dose angiotensin II (ANG II).Methods: Rats were fed high salt (HS) diet (4% NaCl) for 3 days or 4 weeks before return to LS diet for various periods. Other rats fed HS diet (HS + ANG II) received a chronic (3 days) i.v. infusion of a low dose of ANG II (5 ng·kg −1 ·min −1 ) to prevent salt-induced ANG II suppression.Results: HS diet eliminated the increase in cerebral blood flow in response to acetylcholine (ACh) infusion and the relaxation of MCA in response to ACh, iloprost, cholera toxin, and reduced PO 2 . Recovery of vascular relaxation was slow, requiring at least 2 weeks of LS diet, regardless of the duration of exposure to HS diet. Hypoxic dilation was mediated by cyclooxygenase metabolites and ACh-induced dilation was mediated via NO in LS rats and in HS rats returned to LS diet or receiving ANG II infusion. Conclusions:Return to LS diet for 2 weeks or chronic 3-day ANG II infusion restore the mechanisms that normally mediate cerebral vascular relaxation.

Acute and chronic angiotensin-(1–7) restores vasodilation and reduces oxidative stress in mesenteric arteries of salt-fed rats

“…The ability of acute exposure to ANG-(1-7) and AVE-0991 [in addition to chronic infusion of ANG-(1-7)] to reduce vascular superoxide levels and our Western blots of Cu/Zn SOD and MnSOD in HS diet-fed rats receiving ANG-(1-7) infusion indicate that the antioxidant effect of mas receptor activation does not depend on the upregulation of antioxidant enzyme expression at the protein level. This is contrary to the protective effects of chronic low-dose ANG II infusion to prevent the downregulation of Cu/Zn SOD in cerebral arteries of HS diet-fed rats (30). Instead, the findings of the present study suggest that the protective effect of ANG-(1-7) to restore vascular relaxation and reduce superoxide levels in rats fed a HS diet may be due to a number of factors, including the liberation of NO (18,53) in amounts sufficient to quench superoxide radicals, reductions in NADPH oxidase activity (5,9), and/or acute increases in the activity of antioxidant enzymes such as SOD (54).…”

AT1 Receptors Prevent Salt-Induced Vascular Dysfunction in Isolated Middle Cerebral Arteries of 2 Kidney-1 Clip Hypertensive Rats

“…Low-dose ANG II infusion also prevents the downregulation of Cu/Zn SOD in cerebral arteries of Sprague-Dawley rats fed an HS diet. 31 Consistent with the hypothesis that AT 1 receptor activation maintains antioxidant defenses are recent findings that losartan blocks the protective effect of ANG II infusion to reduce vascular superoxide levels and restore arteriolar dilation in hamsters fed an HS diet. 32 In this study, Cu/Zn SOD expression was significantly higher in arteries of 2K1C rats fed an HS diet vs. sham-operated controls fed an HS diet and was not downregulated by an HS diet in the 2K1C rats.…”

Impaired relaxation of cerebral arteries in the absence of elevated salt intake in normotensive congenic rats carrying the Dahl salt-sensitive renin gene

“…Other studies suggest that low-dose ANG II infusion prevents the downregulation of the crucial antioxidant enzyme Cu/Zn SOD in cerebral arteries of normotensive Sprague-Dawley rats fed a HS diet (30). This finding is particularly significant in light of multiple studies showing that a HS diet increases oxidative stress in the vasculature and reduces antioxidant enzyme expression and activity (21-23, 56 -58).…”