SUMMARY 1. The aim of the present study was to clarify the role of 1-adrenoceptors in the mechanism of ischaemic precondition- ing (IP). 2. Rat isolated perfused hearts were either non- preconditioned, preconditioned with 5 min ischaemia or treated for 5 min with 1-adrenoceptor agonists (50 mol/L phenyl- ephrine; 0.1, 0.5 and 1 mol/L methoxamine) before being sub- jected to 45 min of sustained ischaemia followed by 60 min reperfusion. 3. Within each of the above protocols, hearts were divided into groups to which 1-adrenoceptor antagonists (prazosin, 5-methyl urapidil and chloroethylclonidine (CEC)) were admin- istered. Functional recovery and infarct size were used as indices of the effects of ischaemia. Ischaemic contracture characteristics and maximal diastolic pressure during reflow were also assessed. 4. Blockade of 1-adrenoceptors with prazosin or the subtype- selective antagonists 5-methyl urapidil and CEC did not abol- ish the protective effect of IP with respect to both functional recovery and infarct size reduction. 5. Protection afforded by phenylephrine was attenuated in hearts treated with prazosin or the 1B-adrenoceptor- selective antagonist CEC, but not in those treated with the 1-adrenoceptor-selective antagonist 5-methyl urapidil. 6. Treatment with low concentrations of methoxamine, considered to be 1-adrenoceptor selective, did not confer any protection to the ischaemic myocardium. 7. A close relationship between accelerated ischaemic contrac- ture and enhanced cardioprotection was observed. 8. The results suggest that 1-adrenoceptor stimulation mimics IP, but it is not an essential component in the mechan- ism behind the protective effect of IP in rat heart. In addition, the present study demonstrates that stimulation of the 1B- but not the 1A-adrenoceptor subtype is responsible for the catecholamine-induced protection of ischaemic myocardium in rat. Key words: 1-adrenoceptors, ischaemia, preconditioning, rat heart. INTRODUCTION Brief periods of acute myocardial ischaemia protect the heart against subsequent episodes of prolonged ischaemia. Since Murry et al. 1 first demonstrated the phenomenon in a canine model, ischaemic preconditioning (IP) has been extensively studied by a number of investigators. The potent endogenous cardioprotective effects afforded by IP, especially enhancing myocardial cellular survival against irreversible damage caused by ischaemia/reperfusion, have been found consistently in different experimental models, including dogs, 1–4 pigs, 5,6 rabbits, 7–11 rats 12–17 and mice, 18,19 both in vitro and in vivo. However, the exact mechanism involved in IP remains unclear, although a number of receptors, end-effectors or mediating pathways have been suggested to be related to the signal transduc- tion. These include adenosine receptors, 1-adrenoceptors, the pro- tein kinase C (PKC) pathway, ATP-sensitive potassium channels and tyrosine phosphorylation. Nevertheless, there is some controversy regarding these mechanisms, particularly across different animal species. 20,21 There is a considerable amount of evidence supporting the hypoth- esis that 1-adrenoceptor stimulation is an important component mechanism in the protection afforded by preconditioning. It has been shown that 1-adrenoceptor agonists, substituting for IP, protect against postischaemic myocardial dysfunction, 15,22 reduce infarct size 9,23,24 and reduce the incidence of reperfusion-induced ventricu- lar fibrillation and ventricular tachycardia. 25 However, other studies could not provide evidence for the involvement of either endogen- ous catecholamines or stimulation of 1-adrenoceptors in the atten- uation of contractile dysfunction and reduction of infarct size associated with preconditioning. 26–28 Much of the controversy con- cerning the involvement of 1-adrenoceptors in the mechanism of preconditioning results from the fact that most studies use different species, experimental approaches and conditions. To our knowledge, none of the previous studies has investigated both IP and precon- ditioning by 1-adrenoceptor stimulation by means of multiple end- points in the same experimental model. In an attempt to clarify the role of 1-adrenoceptor stimulation in the mechanism of IP in rat heart, we investigated, using 1-adrenoceptor agonists and antagonists whether 1-adrenoceptor stimulation mimics the protection of IP, whether IP is dependent on 1-adrenoceptors to mediate protection and whether these effects are mediated by a particular subtype of 1-adrenoceptors. Postischaemic functional recovery and infarct size were used as end- points. In addition, the development of ischaemic contracture during sustained ischaemia under all protocols used was assessed, because it is known that both IP and preconditioning with catecholamines cause a paradoxical exacerbation of ischaemic contracture. 29,30 ACTIVATION OF  1 -ADRENOCEPTORS IS NOT ESSENTIAL FOR THE MEDIATION OF ISCHAEMIC PRECONDITIONING IN RAT HEART E Vasara, S Seraskeris and A Lazou Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece Correspondence: Dr A Lazou, Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki 54006, Greece. Email: lazou@bio.auth.gr Received 4 May 2001; accepted 1 August 2001. Clinical and Experimental Pharmacology and Physiology (2002) 29, 11–17