Chronic HgCl2 treatment increases vasoconstriction induced by electrical field stimulation: role of adrenergic and nitrergic innervation

Abstract

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.

Effect of short- and long-term portal hypertension on adrenergic, nitrergic and sensory functioning in rat mesenteric artery

“…We have previously reported that in this strain sensory innervation does not participate in vasomotor response induced by EFS in control animals, but that the participation of this innervation is increased in several pathological conditions such as hypertension, cirrhosis and diabetes [12,15,40,41]. In the present study, we observed that pre-incubation with the CGRP antagonist CGRP-(8-37) did not modify the vasoconstrictor response to EFS in mesenteric rings from SO rats, confirming CGRP non-participation in vasoconstriction in healthy Wistar rats [10,36,42]. However, CGRP-(8-37) increased the vasoconstrictor response to EFS in segments from PH rats.…”

Aerobic exercise training increases neuronal nitric oxide release and bioavailability and decreases noradrenaline release in mesenteric artery from spontaneously hypertensive rats

“…Nitric oxide release was measured using fluorescence emitted by the fluorescent probe 4,5-diaminofluorescein (DAF-2), as previously described [25,26]. Endotheliumdenuded mesenteric arteries from sedentary and trained SHRs were subjected to a 60-min equilibration period in HEPES buffer (in mmol/l: NaCl 119; HEPES 20; CaCl 2 1.2; KCl 4.6; MgSO 4 1; KH 2 PO 4 0.4; NaHCO 3 5; glucose 5.5; Na 2 HPO 4 0.15; pH 7.4) at 378C.…”

“…Superoxide anion levels were measured using lucigenin chemiluminescence, as previously described [26]. Endothelium-denuded mesenteric segments from both groups of rats were rinsed in KHS for 30 min, equilibrated for 30 min in HEPES buffer at 378C, transferred to test tubes that contained 1 ml HEPES buffer (pH 7.4) containing lucigenin (5 mmol/l) and then kept at 378 C. The luminometer was set to report arbitrary units of emitted light; repeated measurements were collected for 5 min at 10-s intervals and averaged.…”

Avances en la etiopatogenia de la hipertensión arterial: actualización en la investigación preclínica

“…El tratamiento con rosuvastatina revirtió tales cambios, aportando un nuevo papel regulador neural de las estatinas en el tono vascular 16 . En otro estudio reciente, se ha demostrado que en animales de experimentación el tratamiento con mercurio en bajas dosis, similar al mercurio de las amalgamas dentales, aumenta la respuesta vasoconstrictora a estímulos eléctricos debido, al menos en parte, a una reducción en la biodisponibilidad del NO y a un aumento de la función adrenérgica 17 . Tales resultados aportarían más evidencias sobre el mercurio como factor de riesgo medioambiental en la enfermedad cardiovascular.…”

“…Estabilización de la placa 7 TWEAK/sCD136 Asociación entre la reducción de los niveles séricos y aumento de la mortalidad CV en pacientes con EAP 10,11 Fibulina-5 Involucrada en la respuesta adaptativa de supervivencia en hipoxia 12 CCL-20 Biomarcador que aumenta en pacientes con mayor RCV 11 Adiponectina Activación de la proliferación de células endoteliales 13 Prostaciclina Mayor participación en modelos de hipertensión portal 14,15 Estatinas Efectos pleiotrópicos en la regulación del tono vascular. Prevención del remodelado y mejora de la función cardiaca 16,50 Mercurio Factores de riesgo medioambientales en la enfermedad CV 17 Glitazonas Mejora la disfunción vascular 18---21 Angiotensina II Alteraciones estructurales y funcionales en arterias de resistencia, aumento de estrés oxidativo 22---24…”