Angiotensin IV induced contractions in human jejunal wall musculature in vitro

Angiotensin II (AngII) has been reported to mediate contractile actions in rats and human jejunal wall musculature. However, except for one report showing the angiotensin IV (AngIV) contractile effects on the internal anal sphincter of rats, no data is available describing the action of AngIV on smooth muscle in human small intestine. The aim of this study was to investigate the expression and localization of the enzymes responsible to AngIV formation, as well as the receptor, and to elucidate the contractile function of AngIV in the muscular layer of human jejunum in vitro. Jejunal smooth muscle was taken from 23 patients undergoing Roux-en-Y gastric bypass surgery and was used to record isometric tension in vitro in response to AngIV alone and in the presence of losartan or PD123319. ELISA, western blot and immunohistochemistry were used to investigate the expression and localization of key components for AngIV formation: the enzymes aminopeptidases-A, B, M, and the AngIV receptor insulin-regulated aminopeptidase (IRAP). AngIV elicited concentration-dependent contraction in both longitudinal and circular smooth-muscle preparation. Presence of losartan abolished AngIV-induced contraction, but not PD123319. The main peptide AngII, as well as the enzymes aminopeptidases-A, B and M was detected in all muscle samples. Immunohistochemistry localized the enzymes and IRAP in the myenteric plexus between longitudinal and circular muscle layers. The present study indicates that all enzymes necessary for AngIV formation exist in human jejunal smooth muscle and that the contractile action elicited by AngIV is primarily mediated through the AngII type 1 receptor.