Angiotensin II infusion and reduced salt intake restore normal vasodilator mechanisms in Sprague‐Dawley rats fed a high salt diet

Abstract

Angiotensin II (ANG II) suppression with high salt (HS) diet leads to impaired responses to vasodilator stimuli in normotensive animals. These responses can be restored when HS animals are: (1) returned to a low salt (LS) diet for 2 weeks or (2) infused with a sub-pressor dose of ANG II. The present study determined the mechanisms involved in these restored dilator responses. Male Sprague-Dawley rats were divided into 4 groups: (1) LS diet (0.4% NaCl), (2) 3 day HS diet (4% NaCl), (3) 3 day HS diet followed by 2 week LS diet, and (4) 3 day HS diet followed by 3 day ANG II infusion (5 ng/kg/min, i.v.) while remaining on HS diet. Middle cerebral arteries (MCA) were isolated and cannulated and endothelium-dependent responses to reduced PO2 and acetylcholine (ACh; 1 nM-10 μM) were tested in the presence or absence of 1 μM indomethacin (cyclooxygenase inhibitor) or 100 μM L-NAME (nitric oxide synthase inhibitor). In LS controls and both models of restored vasodilation (return to LS diet and ANG II infusion), responses to hypoxia were eliminated with indomethacin and ACh-induced dilation was eliminated with L-NAME. Impaired responses to iloprost (prostacyclin analogue) and cholera toxin (Gs protein stimulator) were also returned to control values in both models of restored dilation. These observations demonstrate that both 2 weeks of low salt intake and 3 days of ANG II infusion during elevated salt intake restore the mechanisms that normally mediate endothelium-dependent and -independent vasodilation in rat MCA. [NIH #HL-29587; #HL-65289, and #HL-72920].