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Testosterone protects rat hearts against ischaemic insults by enhancing the effects of alpha(1)-adrenoceptor stimulation.


ABSTRACT:

Background and purpose

Testosterone alleviates symptoms in patients with ischaemic heart disease. Androgen receptors are present in the heart, and testosterone upregulates gene expression of cardiac beta(1)-adrenoceptors. We hypothesize that testosterone may confer cardioprotection by interacting with adrenoceptors.

Experimental approach

In isolated perfused hearts and ventricular myocytes from orchidectomized rats without or with testosterone (200 microg/100 g) replacement, we first determined the effect of ischaemia/reperfusion in the presence of noradrenaline (10(-7) M). Then we determined the contribution of interactions between testosterone and alpha(1)- or beta(1)-adrenoceptors in cardiac injury/protection (infarct size, release of lactate dehydrogenase, viability of myocytes, recovery of contractile function and incidence of arrhythmias) upon ischaemia/reperfusion by pharmacological manipulation using selective adrenoceptor agonists (alpha(1)-adrenoceptor agonist: phenylephrine 10(-6) M; non-selective beta-adrenoceptor agonist: isoprenaline 10(-7) M) and antagonists (alpha(1): prazosin or benoxathian 10(-6) M; beta(1): CGP 20712A 5 x 10(-7) M). We also determined the expression of alpha(1) and beta(1)-adrenoceptor in the hearts from rats with and without testosterone.

Key results

Testosterone reduced injury induced by ischaemia/reperfusion and noradrenaline. This was achieved by enhancing the beneficial effect of alpha(1)-adrenoceptor stimulation, which was greater than the deleterious effect of beta(1)-adrenoceptor stimulation (also enhanced by testosterone). The effects of testosterone were abolished or attenuated by blockade of androgen receptors. Testosterone also enhanced the expression of alpha(1A) and beta(1)-adrenoceptor.

Conclusions and implications

Testosterone conferred cardioprotection by upregulating the cardiac alpha(1)-adrenoceptor and enhancing the effects of stimulation of this adrenoceptor. The effect of testosterone was at least partly mediated by androgen receptors.

SUBMITTER: Tsang S 

PROVIDER: S-EPMC2259204 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Publications

Testosterone protects rat hearts against ischaemic insults by enhancing the effects of alpha(1)-adrenoceptor stimulation.

Tsang S S   Wu S S   Liu J J   Wong T M TM  

British journal of pharmacology 20071224 4


<h4>Background and purpose</h4>Testosterone alleviates symptoms in patients with ischaemic heart disease. Androgen receptors are present in the heart, and testosterone upregulates gene expression of cardiac beta(1)-adrenoceptors. We hypothesize that testosterone may confer cardioprotection by interacting with adrenoceptors.<h4>Experimental approach</h4>In isolated perfused hearts and ventricular myocytes from orchidectomized rats without or with testosterone (200 microg/100 g) replacement, we fi  ...[more]

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