Cardiovascular effects of centrally applied endothelin-11–31 and its relationship to endothelin-11–21 in rats

Endothelin-11–31 (ET-11–31) is a novel member of the endothelin family, which comprises 31 amino acids and derived from the selective hydrolysis of big ET-1 by chymase. Although ET-11–31 has been reported to be involved in biological effects via direct or indirect (converting to ET-11–21) mechanisms, the cardiovascular effects of central ET-11–31 are not fully identified. The present study was designed to comparatively investigate the cardiovascular effects of intracerebroventricular (icv) application of ET-11–31 or ET-11–21 in anesthetized rats. Injection (icv) of ET-11–31 (500 pmol) produced a biphasic blood pressure response: an initial increase (from 118 ± 8 to 138 ± 14 mmHg, P < 0.05) followed by a sustained decrease in BP (from 118 ± 8 to 58 ± 9 mmHg, P < 0.05), which was very similar to BP response to icv injection of big ET-1 (500 pmol) or ET-11–21 (25 pmol). The cardiovascular effects of icv injection of ET-11–31 or ET-11–21 were completely antagonized by ETA receptor antagonist BQ123 but not ETB receptor antagonist BQ788. Furthermore, pretreatment with ET converting enzyme inhibitor phosphoramidon (10 nmol) abolished the cardiovascular effects evoked by icv injection of ET-11–31 or big ET-1. In conclusion, the current data showed that central ET-11–31 produced the similar cardiovascular effects as those of central ET-11–21, and suggesting that the central cardiovascular effects of ET-11–31 resulted from it converting to ET-11–21 and then activating ETA receptors.