Drenjancevic-Peric, Ines, and Julian H. Lombard. Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation. Am J Physiol Heart Circ Physiol 287: H957-H962, 2004. First published March 18, 2004 10.1152/ajpheart.01087.2003.-To evaluate the potential role of impaired reninangiotensin system (RAS) function in contributing to reduced vascular relaxation in Dahl salt-sensitive (S) rats, responses to ACh (10 Ϫ6 mol/l) and hypoxia (PO2 reduction to 40 -45 mmHg) 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 a low-salt (LS) diet (0.4% NaCl) dilated in response to ACh and hypoxia, whereas dilation in response to these stimuli was absent in Dahl S rats on LS diet. Vasodilation to ACh and hypoxia was restored in SS-13 BN rats on an LS diet but not in SS-16 BN rats. High-salt diet (4% NaCl), to suppress ANG II, eliminated vasodilation to hypoxia and ACh in BN and in SS-13 BN rats. Treatment of SS-13 BN rats with the AT1 receptor antagonist losartan also eliminated the restored vasodilation in response to ACh 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.hypertension; vascular smooth muscle; renin-angiotensin system; physiological genomics THE RAT IS A WELL-ESTABLISHED experimental model for studies of physiological control mechanisms and pathophysiological conditions, including hypertension. Vascular control mechanisms have been studied extensively in resistance arteries and microvessels of several commonly used inbred and outbred strains of normotensive rats, and in many rat models of hypertension. However, it is now known that different strains of rats exhibit substantial differences in physiological control mechanisms, and these differences can provide valuable information about the genetic basis for various pathophysiological conditions. For example, resistance to global myocardial ischemia is twofold greater in hearts of Brown Norway (BN) rats compared with those of Dahl salt-sensitive (Dahl S) rats (3). In that study, infarct size and postischemic leakage of lactate dehydrogenase were significantly less, and recovery of coronary flow rate and rate-pressure product were significantly faster in BN vs. Dahl S rats. Other studies have shown that BN rats exhibit normal regulation of the renin-angiotensin system (RAS) when dietary salt intake is changed, whereas Dahl S rats have an impaired ability to regulate their RAS (1, 6).Although genetic linkage analysis of blood pressure differences among various strains of rats provides valuable clues regarding the possible role of different genes in contributing to the development and maintenance of hypertension (7,22,25,35), simplified models such as co...