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

Objective: This study determined the mechanisms and time-course of recovery of vascular relaxation in middle cerebral arteries (MCAs) of salt-fed Sprague-Dawley rats returned to a low-salt (LS) diet (0.4% NaCl) or infused with low-dose angiotensin II (ANG II). Methods: Rats were fed a high-salt (HS) diet (4% NaCl) for 3 days or 4 weeks before returning to an LS diet for various periods. Other rats fed a HS diet (HS+ANG II) received a chronic (3 days) intravenous (i.v.) infusion of a low dose of ANG II (5 ng kg-1 min-1) to prevent salt-induced ANG II suppression. Results: The 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 PO2. Recovery of vascular relaxation was slow, requiring at least 2 weeks of the LS diet, regardless of the duration of exposure to a HS diet. Hypoxic dilation was mediated by cyclo-oxygenase metabolites and ACh-induced dilation was mediated via nitric oxide in LS rats and in HS rats returned to the LS diet or receiving ANG II infusion. Conclusions: Returning to a LS diet for 2 weeks or chronic 3-day ANG II infusion restores the mechanisms that normally mediate cerebral vascular relaxation.