Dieta hipossódica aumenta a biodisponibilidade de NO e a produção de prostanóides vasoconstrictores da COX-2 em ratos espontaneamente hipertensos

Abstract

Background and purpose: Salt restriction is recommended for hypertension treatment to reduce blood pressure, but its cardiovascular risk factor implication is still a matter of discussion. The ability of dietary sodium restriction to reduce the incidence of cardiovascular mortality and vascular function in spontaneously hypertensive rats (SHR) is still unclear. The aim of this study was to observe the effect of a long period of salt restriction on the vascular reactivity properties of mesenteric arteries of SHRs. Experimental approach: Male SHR received standard salt diet (0,3 % NaCl) or low salt (0,03 % NaCl) for 28 weeks. Isolated mesenteric artery segments were used to analyze nitric oxide (NO), cyclooxygenase-2 (COX-2) and renin- angiotensin system influence on vascular reactivity. Key results: SHRs at low salt diet had a lower systolic blood pressure (SBP) than rats receiving standard salt diet (low salt: 169±4 mmHg, standard salt: 203±4,7 mmHg; P < 0.05). Low salt intake did not change the phenylephrine-induced vasoconstriction but increase acetylcholine-induced vasodilatation. It also increased the effects of NO synthase inhibition with LNAME (100 mM) on phenylephrine responses and iNOS expression was increased in low salt group. The cyclooxygenase inhibitor, indomethacin (10 µM) and the COX-2 inhibitor NS 398 (1 μM) reduced the reactivity to phenylephrine in low salt treated group and COX-2 protein expression was increased in low salt. The effects of apocynin (10 μM); the superoxide anion scavenger, tiron (1 mM); the hydrogen peroxide scavenger, catalase (1000 U∙mL−1); and the ACE and AT1 receptor blockers, enalapril (10 µM) and losartan (10 µM) on vascular reactivity were not different between the two groups. The level of AT1 protein expression was similar in all groups. Conclusions: These findings suggest that low salt diet modulates mesenteric vasoreactivity response probably by increased NO bioavailability and vasoconstrictor prostanoid production through the COX-2 pathway, respectively in spontaneously hypertensive rats. ROS and the local renin-angiotensin system are not involved in the vascular response.