Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation.
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 ACh (10(-6) mol/l) and hypoxia (Po(2) 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 AT(1) 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.
Drenjancevic-Peric
Ines
I
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Lombard
Julian H
JH
D000109:Acetylcholine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology; D002875:Chromosomes / Q000235:genetics*; D004039:Diet, Sodium-Restricted; D006824:Hybridization, Genetic; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012083:Renin / Q000235:genetics*; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics*; D014665:Vasodilator Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D014665:Vasodilator Agents; D012083:Renin; D019808:Losartan; D000109:Acetylcholine