High salt intake does not produce additional impairment in the coronary artery relaxation of spontaneously hypertensive aged rats.

The effect of a salt-based diet on the coronary responsiveness in aged hypertensive rats (SHR) still is unclear. We investigated the effects of high salt intake on the relaxation properties of coronary arteries of aged SHRs. Male SHR (32 week-old) received drinking water (SHR) or 1% NaCl solution (SHR-Salt) for 8 weeks. Isolated coronary segments were subjected to concentration-response curves to acetylcholine (ACh) in the presence or absence of L-NAME (100 µM), enalaprilate (10 µM), losartan (10 µM), and spironolactone (100 µM). Salt intake did not increase blood pressure in old SHRs, but caused ventricular hypertrophy. The endothelium-dependent relaxation in SHRs was lower than in Wistar rats. However, salt intake did not add further impairment. Both enalaprilate and losartan reduced the vasodilator response in coronary arteries from Wistar, but did not affect SHR-salt rats. Conversely, losartan attenuated the impaired ACh relaxation observed in SHR. Spironolactone reduced the relaxation induced by ACh in coronary arteries from Wistar rats but not in SHR. The renin-angiotensin-aldosterone system participates in the impaired coronary relaxation in aged SHR, but does not partake in this deleterious effect under increased salt intake, indicating that age could differentiate the effects of high sodium intake in coronary arteries of SHR.

Chronic HgCl(2) treatment increases vasoconstriction induced by electrical field stimulation: role of adrenergic and nitrergic innervation.

In the present study, we have investigated the possible changes in rat mesenteric artery vascular innervation function caused by chronic exposure to low doses of HgCl(2) (mercuric chloride), as well as the mechanisms involved. Rats were divided into two groups: (i) control, and (ii) HgCl(2)-treated rats (30 days; first dose, 4.6 µg/kg of body weight; subsequent dose, 0.07 µg·kg-1 of body weight·day-1, intramuscularly). Vasomotor response to EFS (electrical field stimulation), NA (noradrenaline) and the NO donor DEA-NO (diethylamine NONOate) were studied, nNOS (neuronal NO synthase) and phospho-nNOS protein expression were analysed, and NO, O(2)- (superoxide anion) and NA release were also determined. EFS-induced contraction was higher in the HgCl(2)-treated group. Phentolamine (1 µmol/l) decreased the response to EFS to a greater extent in HgCl(2)-treated rats. HgCl(2) treatment increased vasoconstrictor response to exogenous NA and NA release. L-NAME (N(G)-nitro-L-arginine methyl ester; 0.1 mmol/l) increased the response to EFS in both experimental groups, but the increase was greater in segments from control animals. HgCl(2) treatment decreased NO release and increased O(2)- production. Vasodilator response to DEA-NO was lower in HgCl(2)-treated animals. Tempol increased DEA-NO-induced relaxation to a greater extent in HgCl(2)-treated animals. nNOS expression was similar in arteries from both experimental groups, whereas phospho-nNOS was decreased in segments from HgCl(2)-treated animals. HgCl(2) treatment increased vasoconstrictor response to EFS as a result of, in part, reduced NO bioavailability and increased adrenergic function. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.

Endothelial dysfunction of rat coronary arteries after exposure to low concentrations of mercury is dependent on reactive oxygen species.

BACKGROUND AND PURPOSE: Exposure to mercury is known to increase cardiovascular risk but the underlying mechanisms are not well explored. We analysed whether chronic exposure to low mercury doses affects endothelial modulation of the coronary circulation. EXPERIMENTAL APPROACH: Left coronary arteries and hearts from Wistar rats treated with either HgCl(2) (first dose 4.6 µg·kg(-1) , subsequent doses 0.07 µg·kg(-1) day(-1) , 30 days) or vehicle were used. Endothelial cells from pig coronary arteries incubated with HgCl(2) were also used. KEY RESULTS: Mercury treatment increased 5-HT-induced vasoconstriction but reduced acetylcholine-induced vasodilatation. It also reduced nitric oxide (NO) production and the effects of NO synthase inhibition with L-NAME (100 µmol·L(-1) ) on 5-HT and acetylcholine responses. Superoxide anion production and mRNA levels of NOX-1 and NOX-4 were all increased. The superoxide anion scavenger tiron (1 mmol·L(-1)) reduced 5-HT responses and increased acetylcholine responses only in vessels from mercury-treated rats. In isolated hearts from mercury-treated rats, coronary perfusion and diastolic pressure were unchanged, but developed isovolumetric systolic pressure was reduced. In these hearts, L-NAME increased coronary perfusion pressure and diastolic pressure while it further reduced developed systolic pressure. CONCLUSIONS AND IMPLICATIONS: Chronic exposure to low doses of mercury promotes endothelial dysfunction of coronary arteries, as shown by decreased NO bioavailability induced by increased oxidative stress. These effects on coronary function increase resistance to flow, which under overload conditions might cause ventricular contraction and relaxation impairment. These findings provide further evidence that mercury, even at low doses, could be an environmental risk factor for cardiovascular disease.