Receptor-mediated contraction of aortic valve leaflets

Background and aim of the study: The mechanisms that regulate the function of the aortic valve are not fully understood. Cusp tissue has been shown to have contractile properties, but little is known as to which receptors med iate these effects. Methods: We have examined, using isolated organ baths, the response of porc ine aortic valve leaflets to a range of vasoactive agents including endothe lin-1, noradrenaline, adrenaline, the thromboxane (TX) A(2) mimetic U46619, 5-hydroxytryptamine (5-HT), histamine and angiotensin II. The viability of each individual leaflet was rested by the addition of 90 mM KCl. Results: All agents tested, with the exception of angiotensin II, were capa ble of inducing concentration-dependent contractions of the valve leaflets. The responses to endothelin-1 and U46619 were significantly greater than t hose of all the other agents tested. Responses to endothelin-1 could be inh ibited by 10(-5) M of the mixed ETA/B receptor antagonist bosantan. The res ponse to both catecholamines was blocked by 10(-6) M yohimbine, but not by 3 x 10(7) M prazosin, indicating the presence of alpha(2)-adrenoceptors. Th e response to histamine was mediated exclusively by H-1-receptors, as judge d by the antagonistic effect of 10(-6) M of the H-1-receptor antagonist mep yramine. The response to 5-HT could be blocked by 10(-6) M of the 5-HT2A-re ceptor antagonist ketanserin, and that of U46619 by 10(-6) M of the TXA(2)- receptor antagonist SQ30741. Conclusion: These results demonstrate the range of receptor systems that ca n mediate contraction of aortic valve leaflets. Further studies are require d to elucidate the role of these receptors in the physiology and pathophysi ology of the aortic valve.