Participation of voltage-gated sodium and calcium channels in the acute cardiac effects of toluene.

Inhaling solvents can lead to occurrence of cardiac arrhythmias and sudden sniffing death. Mechanisms related to this phenomenon are not fully understood. The purpose of this study was to investigate the effect of acute toluene exposure on heart reactivity to epinephrine and the participation of voltage-gated sodium and calcium channels. We found that acute toluene exposure increased perfusion pressure, left ventricular developed pressure, and heart rate. These actions were inhibited by lidocaine and nifedipine. Our results suggest that acute toluene exposure modify voltage-gated sodium and calcium channel function and expression likely due to a cardiac adrenergic mechanism and these effects could be participating, at least in part, in the presence of cardiac arrhythmias. To our best knowledge, this is the first report to establish a direct participation of voltage-gated Na+ and Ca2+ channels, toluene and epinephrine on cardiac function in rats.

Angiotensin-II type 1 receptor (AT1R) and alpha-1D adrenoceptor form a heterodimer during pregnancy-induced hypertension.

Pregnancy courses with low response to angiotensin II and adrenergic agonists. In preeclampsia, both effects are reverted. It is known that angiotensin II regulates adrenergic system. It is not known, however, the interaction between both systems receptors. Our aim was to study if AT(1)R and alpha1D adrenoceptor heterodimerize in preeclampsia. We used subrenal aorctic coarctation in pregnant rats. Aortic tissues were prepared for confocal imaging and coimmunoprecipitated for alpha1D and AT(1) receptors. We found that AT(1)R and alpha1D adrenoceptor heterodimerize in both, healthy and preeclamptic groups. In healthy pregnant rats, heterodimer is barely detected. In preeclamptic rats however, we found higher heterodimerization. These results suggest that AT(1)R and alpha1D -adrenoceptor may form heterodimers, and may play a role in preeclampsia.

Captopril therapy decreases both expression and function of alpha-adrenoceptors in pre- hypertensive rat aorta.

1.-- The effects of captopril on alpha(1)-adrenoceptor mRNA and protein and phenylephrine-induced contraction was assessed in aorta of pre-hypertensive spontaneously hypertensive rats. 2.-- Four-week-old SHR and WKY rats were treated with captopril [an angiotensin-converting enzyme (ACE) inhibitor] 3 mg kg(-1) day(-1) for 1 week. 3.-- pA(2) values for BMY 7378, an alpha(1D)-adrenoceptor antagonist, were 8.63-9.20 among the different groups. Schild slopes were close to unity suggesting that contraction was produced primarily by alpha(1D)-adrenoceptor stimulation and was not changed with therapy. 4.-- Alpha(1D)-adrenoceptor mRNA and protein values were higher in pre-hypertensive SHR than in WKY, whereas alpha(1A)-adrenoceptor mRNA was higher in WKY and alpha(1B)-adrenoceptors were similar in both strains, and protein was not significantly different for alpha(1A)- and alpha(1B)-subtypes. 5.-- Captopril decreased maximal contraction in SHR, without having effect in WKY rats, while alpha(1D)-adrenoceptor mRNA was decreased in both rat strains but alpha(1D)-adrenoceptor protein was significantly decreased only in SHR, and increased alpha(1A)-mRNA in SHR, no effect of captopril treatment was observed on alpha(1B)-adrenoceptor mRNA and protein nor on alpha(1A)-adrenoceptor protein. 6.-- These data suggest that ACE inhibition by captopril influences both expression and function of alpha(1D)-adrenoceptors in aorta of pre-hypertensive rats, probably avoiding alpha(1D)-subtype expression by blockade of angiotensin II synthesis.