High fat diet reduces NOS functional activity during vasoconstriction in aorta, but not small mesenteric arteries, from Dahl rats

Abstract

Recently, we reported that Dahl salt‐sensitive rats (DS) become hypertensive when placed on a high fat diet (HF) diet for 4 weeks. Reduced NO bioavailability is associated with hypertension. Therefore, we tested the hypothesis that HF‐induced hypertension in salt sensitive rats enhances vasoconstriction by decreasing NO synthase (NOS) functional activity. DS and normotensive control (SS.BN13) (12 weeks old) were given normal fat (NF) or HF (36% fat) diet for 4 weeks. Dose response curve to phenylephrine (PE: 1 nM to 10 μM) were generated in isolated aorta and 3rd order mesenteric arteries (MA). In both strains, HF did not change the contractile response to PE in aorta (logEC50 of NF vs HF: DS: −7.7±0.1 vs −8.3±0.4, BN13: −7.4±0.1 vs −7.6±0.1) or MA (DS: −6.0±0.1 vs −5.8±0.1, BN13: −6.1±0.1 vs −6.1±0.1). Inhibition of NOS (100 μM of L‐NAME) in both strains on NF increased sensitivity to PE in aorta (L‐NAME logEC50 of NF: DS: −8.0±0.0, BN13: −7.9±0.1; both P<0.01) and MA (DS: −6.6±0.1, BN13: −6.6±0.1; both P<0.001). Interestingly, HF diminished L‐NAME‐induced sensitivity in aorta, but not MA in both strains (L‐NAME logEC50 of HF: aorta: DS −8.0±0.6, P=0.72; BN13: −7.8±0.1, P=0.29; MA: DS −6.2±0.1, P=0.01: BN13: −6.7±0.1, P<0.001). These results indicate that HF reduces the NOS buffering capacity during vasoconstriction in aorta, but not small mesenteric arteries, independent of hypertension.