CARDIAC AND VASCULAR-RESPONSES OF ISOLATED RAT-TISSUES TREATED WITH DITERPENES FROM SINULARIA-FLEXIBILIS (COELENTERATA, OCTOCORALLIA)

The marine environment is a rich source of compounds with cardiovascul ar activity. This study characterizes the cardiac and vascular respons es in isolated rat tissues of flexibilide, dihydroflexibilide and sinu lariolide, three diterpenes isolated from the soft coral Sinularia fle xibilis. On rat left ventricular papillary muscles, dihydroflexibilide and flexibilide showed similar potencies (-log EC(50) = 4.69 +/- 0.05 and 4.66 +/- 0.06, respectively); the maximal response to dihydroflex ibilide of 1.4 +/- 0.2 mN was 35 +/- 7% that of calcium chloride in th e same muscles. All diterpenes relaxed rat thoracic aortic rings preco ntracted with KCl (100 mM) with similar potencies (flexibilide, -log E C(50) = 4.17 +/- 0.06), Flexibilide was further characterized and show n to increase force in isolated rat left atria by 0.8 +/- 0.5 mN at 1 x 10(-4) M, to increase rate of contraction in isolated rat right atri a by 18 +/- 5 beats/min at 3 x 10(-5) M and to completely relax endoth elium-denuded rat thoracic aortic rings (-log EC(50) = 4.14 +/- 0.05), Toxicity as indicated by the occurrence of ectopic beats was not obse rved with the diterpenes at concentrations which produced complete rel axation of blood vessels, maximal positive inotropic activity and mino r positive chronotropic responses, Thus, these compounds may be useful lead compounds in the search for improved treatment of cardiovascular disease, especially heart failure. Copyright (C) 1996 Published by El sevier Science Ltd