Angiotensin II-induced contractions in human jejunal wall musculature in vitro.
OBJECTIVE
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 angiotensin 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 combination, tetrodotoxin (TTX) (10(-6) M), atropine (10(-6) M) and guanethidine (3 x 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.


CONCLUSIONS
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.
Spak
E
E
Department of Gastrosurgical Research, Sahlgrenska Academy, University of Gothenburg, Sweden. emma.spak@gastro.gu.se
Casselbrant
A
A
Olbers
T
T
Lönroth
H
H
Fändriks
L
L
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D046509:Tissue Culture Techniques
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II