Cardiovascular effects of centrally applied endothelin-1 1–31 and its relationship to endothelin-1 1–21 in rats

Abstract

Endothelin-1 1–31 (ET-1 1–31) 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-1 1–31 has been reported to be involved in biological effects via direct or indirect (converting to ET-1 1–21) mechanisms, the cardiovascular effects of central ET-1 1–31 are not fully identified. The present study was designed to comparatively investigate the cardiovascular effects of intracerebroventricular (icv) application of ET-1 1–31 or ET-1 1–21 in anesthetized rats. Injection (icv) of ET-1 1–31 (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-1 1–21 (25 pmol) . The cardiovascular effects of icv injection of ET-1 1–31 or ET-1 1–21 were completely antagonized by ET A receptor antagonist BQ123 but not ET B receptor antagonist BQ788. Furthermore, pretreatment with ET converting enzyme inhibitor phosphoramidon (10 nmol) abolished the cardiovascular effects evoked by icv injection of ET-1 1–31 or big ET-1. In conclusion, the current data showed that central ET-1 1–31 produced the similar cardiovascular effects as those of central ET-1 1–21, and suggesting that the central cardiovascular effects of ET-1 1–31 resulted from it converting to ET-1 1–21 and then activating ET A receptors.