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1 Department of Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
* To whom correspondence should be addressed. E-mail: amoreira{at}med.up.pt.
This study investigated, in rabbit papillary muscles (n=61) and human auricular strips (n=7), effects of endothelin-1 (ET-1; 0.1-10 nM) on diastolic myocardial properties. ET-1 (1 nM) was also given in the presence of: selective ETA or ETB antagonism, non-selective ETA/ETB antagonism and Na+/H+ exchanger inhibition. Effects of 6.3mM Ca2+ were also studied. ET-1 dose-dependently increased inotropism. In contrast to baseline, in presence of ET-1 resting tension (RT) decreased, after an isometric twitch, 3.4±1.4%, 6.9±1.5%, 12.5±3.1% with 0.1, 1 and 10 nM, respectively, reflecting an increase in myocardial distensibility. ET-1 effects were abolished, with selective ETA, as well as non-selective ETA/ETB antagonism, while they were still present with ETB antagonism. Na+/H+ exchanger inhibition abolished ET-1 effects on distensibility, while only partially inhibited positive inotropic effect. Ca2+ increased inotropism to a similar extent than ET-1 (1 nM), but did not affect distensibility. ET-1, therefore, increased diastolic distensibility of acutely loaded human and non-human myocardium. This effect is mediated by ETA receptors, requires Na+/H+ exchanger activation and cannot be elicited by Ca2+.
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