title: Testosterone protects rat hearts against ischaemic insults by enhancing the effects of alpha(1)-adrenoceptor stimulation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Department of Physiology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: S
authors.initials: S
authors.lastname: Tsang
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: T M
authors.initials: TM
authors.lastname: Wong
mesh_terms: D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000378:metabolism*; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000517:prevention & control; D002470:Cell Survival; D017373:Cyproterone Acetate / Q000494:pharmacology; D004195:Disease Models, Animal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000008:administration & dosage / Q000378:metabolism*; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D016277:Ventricular Function, Left
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D000726:Androgen Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D011944:Receptors, Androgen; D013739:Testosterone; D017373:Cyproterone Acetate; D007770:L-Lactate Dehydrogenase; D009638:Norepinephrine