Mechansim of reduced vascular relaxation in aorta from Dahl salt‐sensitive rats on elevated dietary fat

Abstract

Dahl salt‐sensitive (DS) rats on 4 weeks high fat diet (HF; 35%) become hypertensive compared to SS.BN13 controls. This study tested the hypothesis that 4 weeks of HF increases oxidative stress and blunts relaxation in arteries from DS compared to SS.BN13 rats. Thoracic aortae and third order mesenteric arteries are isolated and concentration response curves are performed to acetylcholine (Ach) and sodium nitroprusside (SNP). Ach‐induced relaxation is blunted in aorta from DS compared to SS.BN13 (% max. relaxation: 86 ± 3 vs 66 ± 5; p<0.05). Treatment with L‐NAME (100 μM; NOS inhibitor), abolished relaxation in aorta, and tempol (10 mM; superoxide dismutase mimetic) blunted vasorelaxation in aorta from SS.BN13 only (% max. relaxation: 69 ± 7; p<0.05). Aorta from DS displayed decreased sensitivity to SNP compared to SS.BN13 (logEC50: −8.5 ± 0.1 vs −7.8 ± 0.1; p<0.05). Ach‐ and SNP‐induced relaxations are similar in small mesenteric arteries from both strains. L‐NAME produced a comparable and significant decrease in sensitivity to Ach in arteries from both strains (logEC50: SS.BN13: −6.9 ± 0.2 vs −7.8 ± 0.1, p<0.05; DS: −7.3 ± 0.1 vs −8.2 ± 0.2, p<0.05). Tempol did not alter relaxation in mesenteric arteries. Therefore, HF induces aortic dysfunction in DS which is likely related to reduced NO responsiveness of smooth muscle and decreased dilatory reactive oxygen species, with no dysfunction in small mesenteric arteries.