Low-dose Angiotensin II Infusion Restores Vascular Function in Cerebral Arteries of High Salt-fed Rats by Increasing Copper/zinc Superoxide Dimutase Expression

Background: This study examined the vasoprotective role of circulating angiotensin II (ANG II) levels in the cerebral circulation of high salt (HS)-fed (SS.BN-(D13hmgc41-13hmgc23)/Mcwi) (Ren1-BN) congenic rats, which carry a normally functioning renin allele from the Brown Norway (BN) rat on the Dahl salt-sensitive genetic background.

Methods: Ren1-BN rats were placed on an HS (4.0% NaCl) diet for 3 days. The vasodilator response to acetylcholine (ACh; 10(-10) - 10(-6) mol/L) was assessed in isolated middle cerebral arteries (MCAs), and Western blots were performed to assess the expression of the antioxidant enzymes copper (Cu)/zinc (Zn) superoxide dismutase (SOD) and manganese (Mn) SOD in cerebral resistance vessels. A separate group of HS-fed animals were infused with either a subpressor dose of ANG II (100ng/kg/min) or saline vehicle via osmotic minipump for 3 days.

Results: HS diet eliminated acetylcholine (ACh)-induced dilation in the MCAs of the congenic rats. Western blot analysis of antioxidant enzymes showed that Cu/Zn SOD and Mn SOD expression were significantly reduced in the cerebral resistance arteries of the HS-fed rats compared with control animals fed a normal salt diet. Infusion of ANG II restored the vasodilator response to ACh in the MCAs and increased Cu/Zn SOD (but not Mn SOD) expression compared with saline-infused animals.

Conclusions: These results indicate that prevention of salt-induced ANG II suppression prevents vascular dysfunction in the cerebral circulation by preventing the downregulation of Cu/Zn SOD and vascular oxidant stress that normally occurs with HS diet.