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Background: It is well known that estrogen can modulate distribution and function of adrenergic receptors in the heart of different species. We reported here gender differences in adrenergic responsiveness of electrically driven guinea pig left atria., Methods: Experiments were performed on the guinea pigs divided in four groups: males control (MC), males treated by 17-beta-estradiol (MTE), females control (FC) and females treated by tamoxifen (FTT). After two weeks of treatment, the animals were sacrificed, the left atria were isolated and force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and time to peak contraction (ttp) and relaxation time at 10% of amplitude (tt(10) ) were measured., Results: Apart from significantly lower Fc and longer tt10 in FC (0.97+/-0.12 mN, 233+/-7 ms, respectively) vs. MC (1.66+/-0.3, 176.3+/-18 ms, respectively, n=6, P<0.05), isoprenaline (ISO) and noradrenaline (NOR) (in the presence of prazosine) concentration-response curves were strongly shifted leftward in comparison with male group. Additionally, the maximal effects of. NOR was significantly lower in FC (about 40%) than in MC. Application of 17-beta-estradiol to males and tamoxifen to females guinea pigs confirmed crucial role of estrogen in observed phenomenon., Conclusion: Our results indicate that estrogen not only downregulates beta1-adrenoceptors, but induces its hypersensitivity to catecholamines, at least in guinea pig left atria.

Background: Although ischemic preconditioning (PC) is known to confer cardioprotection in healthy subjects, it is unclear whether this phenomenon exists in the presence of hyperlipidaemia. The goal of this study was to determine whether the cardioprotective effect of PC is affected by hyperlipidaemia in a guinea pig model., Methods: We investigated the influence of preconditioning in normo- and hyperlipidaemic animals on papillary muscle contractility and myocardial damage as expressed by the percentage of apoptotic cells. Guinea pigs were fed a normal diet or a hyperlipidaemic diet for 5 weeks. Experiments were performed on papillary muscles subjected to experimental ischemia-reperfusion with or without prior PC., Results: The dietary treatment resulted in significant changes in lipid parameters, which had not affected the functionality of the right ventricle papillary muscle, both at basal conditions and in response to ischemia-reperfusion injury. However, it was found that the hyperlipidaemic diet had an effect on ischemia-induced apoptosis. Papillary muscles of hyperlipidaemic animals with higher HDL plasma concentrations were less susceptible to ischemia-reperfusion injury., Conclusions: This study demonstrates that hyperlipidaemia does not alter the benefits of ischemic preconditioning such as a reduction of apoptosis and preservation of myocardial contractility. Additionally, it has been shown that plasma HDL may protect cardiomyocytes against ischemia-induced apoptosis.

Background: Recently, gender related differences in heart function have been extensively studied. Some of them, as differences in repolarization between males and females have been explained by direct effect of estrogen on delayed rectifier K+ channels and Ca2+ channels. It seems that estrogen induces overexpression of SUR2A subunits of ATP-sensitive K+ channels. The aim of this paper was to compare heart rate changes in male and female guinea pigs in the presence of different potassium channel openers (PCOs)., Methods: We used spontaneously beating right atria from control and estrogen receptor modulator-treated male and female guinea pigs (17-beta-estradiol as a stimulator and tamoxifen as a blocker of estrogen receptor located in heart muscle)., Results: In control females, rilmakalim and diazoxide, but not pinacidil elicited concentration-dependent decrease of heart rate. On the other hand, all three PCOs induced similar negative chronotropic action in hearts obtained from male control group (Emax was between -40 and -70 bpm, respectively). After two weeks of treatment with 17-beta-estradiol, pinacidil failed to significantly decrease heart rate in males however, tamoxifen-pretreated female group responded by decrease in automatism in the presence of rising concentration of pinacidil (Emax=-45+/-6 bpm, not significantly different from Emax in male control=-40+/-5 bpm, n=7). Interestingly, we observed lower blood concentration of the heart form of lactate dehydrogenase (H-LDH) in female than in male control group. Moreover, H-LDH concentration increased in tamoxifen-pretreated female group and decreased in 17-beta-estradiol-treated male group., Conclusion: Our results indicate that estrogen downregulates H-LDH production and specifically modulate pinacidil action in guinea pig right atria, probably by changes of binding site for this drug in SUR2A receptor, but not for rilmakalim and diazoxide.