Examinando por Autor "Padilha, A"

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Activation of BKCa channels by nitric oxide prevents coronary artery endothelial dysfunction in ouabain-induced hypertensive rats
(2009-01) Briones, AM; Padilha, A; Cogolludo, A; Alonso, MJ; Vassallo, DV; Pérez-Vizcaíno, F; Salaices, M
Objective Chronic-ouabain administration to rats induces hypertension and increases the endothelial modulation of vasoconstrictor responses. The aim of this study was to analyze whether ouabain-treatment affects the mechanisms involved in endothelium-dependent relaxation of coronary arteries. Methods Coronary arteries from control and ouabain-treated rats (aprox 8.0mg/day, 5 weeks) were used. Vascular reactivity was analyzed by isometric tension recording and membrane currents were measured using the whole-cell configuration of the patch-clamp technique. Results In 5-hydroxytryptamine (5-HT) precontracted arteries, acetylcholine (ACh, 1 nmol/l¿10mmol/l) induced a similar relaxant response in coronary arteries from both groups that was abolished by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (100mmol/l). However, when arteries were contracted with high KCl (60 mmol/l) or preincubated with the large-conductance Ca2þ-activated Kþ (BKCa) channels-blocker iberiotoxin (0.1mmol/l), the relaxation elicited by ACh was more reduced in ouabain-treated than control rats. After iberiotoxin preincubation, the relaxant response of the nitric-oxide donor, DEA-NO (10 nmol/l¿100mmol/l) was significantly inhibited in ouabain-treated coronary arteries but not in control vessels. The soluble guanylyl cyclase activator BAY 41-2272 (10 nmol/l¿30mmol/l) induced relaxant responses that were inhibited by iberiotoxin. In coronary-artery myocytes isolated from ouabain-treated rats DEA-NO (1mmol/l) markedly increased the amplitude of the iberiotoxin-sensitive current in the whole range of test potentials, compared with nontreated rats. Conclusion Our results indicate that chronic ouabain treatment increases activation of BKCa currents by nitric oxide and this effect might contribute to preserve the endothelial function in coronary arteries in this hypertension model
Ouabain treatment changes the role of endothelial factors in rat resistance arteries
(2008-12-14) Padilha, A; Pecanha, FM; Vassallo, DV; Alonso, MJ; Salaices, M
This study investigates the participation of the endothelial factors in the ¿ adrenoceptor contractile responses in mesenteric resistance arteries from 15 days ouabain-treated (25 ¿g/kg/day) and untreated rats. Ouabain treatment increased blood pressure and heart rate without changing the contractile response to phenylephrine (3 nM¿30 ¿M). Endothelium removal or NG-nitro-L-arginine methyl ester (L-NAME, 100 ¿M), increased the responses to phenylephrine. The endothelial modulation was similar in both rat groups, but the L-NAME effects were bigger in arteries from ouabain-treated rats. However, the endothelial NOS expression and the relaxation to acetylcholine (0.1 nM¿10 ¿M) remained unaltered after ouabain treatment. The coincubation with L-NAME and indomethacin (100 ¿M) leftward shifted the concentration¿response curves to phenylephrine in arteries from untreated rats similarly to the displacement after incubation only with L-NAME. However, in mesenteric arteries from treated rats, the co-incubation with indomethacin and L-NAME did not alter the response to phenylephrine. The addition of the inhibitor of calcium activated potassium channels tetraethylammonium (2 mM) further leftward shifted the phenylephrine curves only in arteries from untreated rats. Cyclooxygenase-2 (COX-2) expression was greater in vessels from ouabaintreated rats. In conclusion, the chronic ouabain treatment for 15 days modified the participation of endothelial factors in response to phenylephrine in mesenteric resistance arteries, by increasing the release of NO and prostanoids and impairment the endothelium-derived hyperpolarizing factor (EDHF) release. This was accompanied by an increased COX-2 expression. Although this balance avoids changes in the phenylephrine concentration¿response curves, these vascular changes might contribute to maintain the ouabain-induced hypertension.