Angiotensin II-induced contractions in human jejunal wall musculature in vitro E. Spak, A. Casselbrant, T. Olbers, H. Lo ¨nroth and L. Fa ¨ ndriks Department of Gastrosurgical Research, Sahlgrenska Academy, University of Gothenburg, Sweden Received 30 July 2007, revision requested 29 August 2007, revision received 14 November 2007, accepted 2 December 2007 Correspondence: E. Spak (PhD), Department of Gastrosurgical Research, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden. E-mail: emma.spak@gastro.gu.se Abstract Aim: Angiotensin II is well known for its contractile effects on smooth muscle cells. This effect is also present in the gut previously shown in animal models. The aim of this study was to clarify expression and localization of angiotensin II receptors in the human small intestine and to explore the pharmacological profile of angiotensin II effects in vitro. Methods: Strips of jejunal muscle wall from 32 patients undergoing bariatric surgery were used to record isometric tension in vitro in response to angio- tensin II (10 )10 –10 )5 m) alone and in the presence of PD123319 (10 )7 m), losartan (10 )7 m), PD123319 (10 )7 m) and losartan (10 )7 m) in combina- tion, tetrodotoxin (TTX) (10 )6 m), atropine (10 )6 m) and guanethidine (3 · 10 )6 m). Western blot, immunohistochemistry and RT-PCR were performed on corresponding muscle samples to identify expression and localization of key components of the renin–angiotensin system. Results: Angiotensin II elicited concentration-dependent contraction in both longitudinal and circular jejunal muscle wall strips; neither TTX, atropine nor guanethidine affected this action. Losartan alone and in combination with PD123319 shifted the concentration–response curve to the right. Transcription of angiotensinogen, ACE and angiotensin II types 1 and 2 receptor RNA was detected in all patients. Immunohistochemistry detected angiotensin II type 1 receptors in the musculature; both angiotensin II types 1 and type 2 receptors were found in the myenteric plexus. Conclusion: This pharmacological analysis indicates that the contractile action elicited by angiotensin II on jejunal wall musculature is primarily mediated through the angiotensin II type 1 receptor located on the musculature. Keywords renin–angiotensin system, small intestine, smooth muscle con- tractions. The renin–angiotensin system (RAS) with its key medi- ator Ang II is well known for its effects on the vascular smooth musculature and for contributing to extracellu- lar fluid volume and electrolyte homeostasis (De Gas- paro et al. 2000). Although the digestive system has a great impact on the latter, only few reports deal with angiotensin II (Ang II)-elicited effects on the gut. It has been shown that mucosal net fluid and buffer transport are markedly influenced by the RAS (Levens 1985, Johansson et al. 1997, 2001, Jin et al. 1998, 1999). Actions on the muscular wall of the gastrointestinal tract have also been demonstrated (Godfraind et al. 1966, Beleslin 1968, Turker & Ercan 1978, Weekley 1990, Schinke et al. 1991, Fan et al. 2002). A recent study from our laboratory reported Ang II type 1 receptor (AT1R)-mediated contractions of the human oesophagus and lower oesophageal sphincter in vitro and showed that there is an AT1R-dependent component of the peristaltic contraction force following swallowing in vivo (Casselbrant et al. 2007). Another Acta Physiol 2008, 193, 181–190 Ó 2008 The Authors Journal compilation Ó 2008 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2007.01826.x 181