Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation

Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H957-62. doi: 10.1152/ajpheart.01087.2003. Epub 2004 Mar 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Angiotensin II Type 1 Receptor Blockers
  • Animals
  • Cerebral Arteries* / drug effects
  • Cerebral Arteries* / physiopathology
  • Chromosomes / genetics*
  • Diet, Sodium-Restricted
  • Hybridization, Genetic*
  • Hypoxia / physiopathology
  • In Vitro Techniques
  • Losartan / pharmacology
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Dahl
  • Renin / genetics*
  • Vasodilation / drug effects
  • Vasodilation / genetics*
  • Vasodilator Agents / pharmacology

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Vasodilator Agents
  • Renin
  • Losartan
  • Acetylcholine