Introgression of Chromosome 13 into the Dahl S Genetic Background Restores Cerebral Artery Dilation in SS-13 Consomic Rats

To evaluate the potential role of impaired renin-angiotensin system (RAS) function in contributing to reduced vascular relaxation in Dahl salt sensitive (S) rats, responses to acetylcholine (10-6 mol/L) and hypoxia (PO 2 reduction to 40-45 mm Hg), were determined in isolated middle cerebral arteries of Dahl S rats, Brown Norway (BN) rats, and consomic rats having chromosome 13 (containing the renin gene) or chromosome 16 of the BN rat substituted into the Dahl S genetic background (SS-13 BN and SS-16 BN , respectively). Arteries of BN rats on LS diet (0.4% NaCl) dilated in response to acetylcholine and hypoxia, while dilation in response to these stimuli was absent in Dahl S rats on LS diet. Vasodilation to acetylcholine and hypoxia was restored in SS-13 BN rats on LS diet, but not in SS-16 BN rats. High salt diet (4% NaCl), to suppress ANG II, eliminated vasodilation to hypoxia and acetylcholine in BN and in SS-13 BN rats. Treatment of SS.13 BN rats with the AT-1 receptor antagonist losartan also eliminated the restored vasodilation in response to acetylcholine and hypoxia. These studies suggest that restoration of normal RAS regulation in SS-13 BN consomic rats restores vascular relaxation mechanisms that are impaired in Dahl S rats.