Reduced angiotensin II and oxidative stress contribute to impaired vasodilation in Dahl salt-sensitive rats on low-salt diet.
This study investigated the role of impaired angiotensin II (Ang II) modulation in contributing to reduced vascular relaxation in isolated middle cerebral arteries (MCA) (100 to 200 microm in diameter) of normotensive Dahl salt-sensitive (SS) rats maintained on low salt (LS) diet (0.4% NaCl) for 9 to 10 weeks. MCA from SS rats on LS diet (n=6 to 9) constricted in response to reduction of perfusate and superfusate PO2 to 35 to 40 mm Hg or acetylcholine (ACh). Vasodilator responses to reduced PO2 and ACh were restored in SS.13BN consomic rats that are 98% genetically identical to SS rats, but exhibit normal regulation of their renin-angiotensin system (RAS). This restored dilation could be prevented by feeding SS.13BN rats high-salt (HS) diet (4% NaCl) for 3 days to suppress Ang II. A continuous intravenous infusion of a subpressor dose (3 ng/kg per minute) of Ang II for 3 days restored vasodilator responses to ACh and reduced PO2 in SS.13BN rats on HS diet and in SS rats on LS diet. Superoxide scavenging with tempol (100 micromol/L) restored vasodilator responses to ACh and reduced PO2 in MCA of SS rats on LS diet, but did not affect vasodilator responses in MCA of SS.13BN rats on LS diet. These data indicate that exposure to chronically low Ang II levels leads to impaired vascular relaxation in SS rats, even when the animals are on LS diet and normotensive. This impaired relaxation appears to be mediated by increased levels of oxidative stress in the arteries.
Drenjancevic-Peric
Ines
I
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Lombard
Julian H
JH
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D013113:Spin Labels; D013481:Superoxides / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017673:Sodium Chloride, Dietary; D013113:Spin Labels; D014665:Vasodilator Agents; D013481:Superoxides; D000804:Angiotensin II; D000109:Acetylcholine; D010100:Oxygen; C001803:tempol