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Testosterone and cholesterol vasodilation of rat aorta involves L-type calcium channel inhibition.

Alvarez E, Cairrão E, Morgado M, Morais C, Verde I - Adv Pharmacol Sci (2010)

Bottom Line: None of the potassium channel antagonists tested (glibenclamide, tetraethylammonium and 4-aminopyridine) modified significantly the relaxant effect of testosterone.The antagonist of classic testosterone receptors, flutamide, did not modify the vasorelaxant effect of testosterone.These results suggest that the vasodilator mechanism of cholesterol and testosterone is the same.

View Article: PubMed Central - PubMed

Affiliation: CICS-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.

ABSTRACT
Testosterone has rapid nongenomic vasodilator effects which could be involved in protective cardiovascular actions. Several authors suggested specific mechanisms to explain this effect, but this matter was not clarified yet. We studied the actions of testosterone and cholesterol on endothelium-denuded rat aorta and their effects on the L-type Ca(2+) current (I(Ca,L)) and potassium current (I(K)). Testosterone (1-100 μM) totally relaxed, in a rapid and concentration-dependent way, the aortic rings contracted by KCl or by (-)-Bay K8644 (BAY). Cholesterol also fully relaxed the contractions induced by KCl. None of the potassium channel antagonists tested (glibenclamide, tetraethylammonium and 4-aminopyridine) modified significantly the relaxant effect of testosterone. The antagonist of classic testosterone receptors, flutamide, did not modify the vasorelaxant effect of testosterone. Furthermore, testosterone and cholesterol inhibited either basal and BAY-stimulated I(Ca,L) in A7r5 cells and they have no effects on I(K). In summary, our results demonstrate that cholesterol and testosterone relax rat aorta by inhibiting LTCC. This effect of testosterone is not mediated by the classic hormone receptor or by potassium channel activation. These results suggest that the vasodilator mechanism of cholesterol and testosterone is the same.

No MeSH data available.


Related in: MedlinePlus

Effect of potassium channel inhibitors on rat aorta relaxation induced by testosterone. Effect of increasing concentrations of testosterone (1–100 μM) in endothelium-denuded rat aortic rings contracted with KCl (60 mM) in presence or absence of the potassium channel inhibitors glibenclamide (GLI; 10 μM), 4-aminopyridine (4-AP; 1 mM), or tetraethylammonium (TEA; 1 mM). Each point represents the mean value ± SEM (indicated in vertical bars) from the number of experiments shown in brackets.
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fig2: Effect of potassium channel inhibitors on rat aorta relaxation induced by testosterone. Effect of increasing concentrations of testosterone (1–100 μM) in endothelium-denuded rat aortic rings contracted with KCl (60 mM) in presence or absence of the potassium channel inhibitors glibenclamide (GLI; 10 μM), 4-aminopyridine (4-AP; 1 mM), or tetraethylammonium (TEA; 1 mM). Each point represents the mean value ± SEM (indicated in vertical bars) from the number of experiments shown in brackets.

Mentions: The effects of inhibitors of three different potassium channels (glibenclamide, 4-AP, and TEA) were also investigated in order to analyse the involvement of these channels in the relaxant mechanism of testosterone. The presence of glibenclamide, 4-AP or TEA, did not have a significant effect on the contraction induced by KCl (data not show) and did not modify significantly the relaxant effect of testosterone (Figure 2) (P > .05, one-way ANOVA with Dunnet's post hoc test). The IC50 values calculated for testosterone in the presence of anyone of the K+ channel inhibitors did not differ significantly from the IC50 values calculated in the absence of the blockers (P > .05; Table 1).


Testosterone and cholesterol vasodilation of rat aorta involves L-type calcium channel inhibition.

Alvarez E, Cairrão E, Morgado M, Morais C, Verde I - Adv Pharmacol Sci (2010)

Effect of potassium channel inhibitors on rat aorta relaxation induced by testosterone. Effect of increasing concentrations of testosterone (1–100 μM) in endothelium-denuded rat aortic rings contracted with KCl (60 mM) in presence or absence of the potassium channel inhibitors glibenclamide (GLI; 10 μM), 4-aminopyridine (4-AP; 1 mM), or tetraethylammonium (TEA; 1 mM). Each point represents the mean value ± SEM (indicated in vertical bars) from the number of experiments shown in brackets.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990104&req=5

fig2: Effect of potassium channel inhibitors on rat aorta relaxation induced by testosterone. Effect of increasing concentrations of testosterone (1–100 μM) in endothelium-denuded rat aortic rings contracted with KCl (60 mM) in presence or absence of the potassium channel inhibitors glibenclamide (GLI; 10 μM), 4-aminopyridine (4-AP; 1 mM), or tetraethylammonium (TEA; 1 mM). Each point represents the mean value ± SEM (indicated in vertical bars) from the number of experiments shown in brackets.
Mentions: The effects of inhibitors of three different potassium channels (glibenclamide, 4-AP, and TEA) were also investigated in order to analyse the involvement of these channels in the relaxant mechanism of testosterone. The presence of glibenclamide, 4-AP or TEA, did not have a significant effect on the contraction induced by KCl (data not show) and did not modify significantly the relaxant effect of testosterone (Figure 2) (P > .05, one-way ANOVA with Dunnet's post hoc test). The IC50 values calculated for testosterone in the presence of anyone of the K+ channel inhibitors did not differ significantly from the IC50 values calculated in the absence of the blockers (P > .05; Table 1).

Bottom Line: None of the potassium channel antagonists tested (glibenclamide, tetraethylammonium and 4-aminopyridine) modified significantly the relaxant effect of testosterone.The antagonist of classic testosterone receptors, flutamide, did not modify the vasorelaxant effect of testosterone.These results suggest that the vasodilator mechanism of cholesterol and testosterone is the same.

View Article: PubMed Central - PubMed

Affiliation: CICS-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.

ABSTRACT
Testosterone has rapid nongenomic vasodilator effects which could be involved in protective cardiovascular actions. Several authors suggested specific mechanisms to explain this effect, but this matter was not clarified yet. We studied the actions of testosterone and cholesterol on endothelium-denuded rat aorta and their effects on the L-type Ca(2+) current (I(Ca,L)) and potassium current (I(K)). Testosterone (1-100 μM) totally relaxed, in a rapid and concentration-dependent way, the aortic rings contracted by KCl or by (-)-Bay K8644 (BAY). Cholesterol also fully relaxed the contractions induced by KCl. None of the potassium channel antagonists tested (glibenclamide, tetraethylammonium and 4-aminopyridine) modified significantly the relaxant effect of testosterone. The antagonist of classic testosterone receptors, flutamide, did not modify the vasorelaxant effect of testosterone. Furthermore, testosterone and cholesterol inhibited either basal and BAY-stimulated I(Ca,L) in A7r5 cells and they have no effects on I(K). In summary, our results demonstrate that cholesterol and testosterone relax rat aorta by inhibiting LTCC. This effect of testosterone is not mediated by the classic hormone receptor or by potassium channel activation. These results suggest that the vasodilator mechanism of cholesterol and testosterone is the same.

No MeSH data available.


Related in: MedlinePlus