Angiotensin II induced contraction of rat and human small intestinal wall musculature in vitro.
BACKGROUND
Angiotensin II (Ang II) is a well-known activator of smooth muscle in the vasculature but has been little explored with regard to intestinal wall muscular activity. This study investigates pharmacological properties of Ang II and expression of its receptors in small-intestinal smooth muscle from rats and humans.


METHODS
Isometric recordings were performed in vitro on small intestinal longitudinal muscle strips. Protein expressions of Ang II typ 1 (AT1R) and typ 2 (AT2R) receptors were assessed by Western blot.


RESULTS
Ang II elicited concentration-dependent contractions of rat jejunal and ileal muscle preparations. The concentration-response curve (rat ileum, EC(50): 1.5 +/- 0.9 x 10(-8) M) was shifted to the right by the AT1R receptor antagonist losartan (10(-7) M) but was unaffected by the AT2R antagonist PD123319 (10(-7) M) as well as by the adrenolytic guanethidine (3 x 10(-6) M) and the anticholinergic atropine (10(-6) M). Human duodenal, jejunal and ileal longitudinal muscle preparations all contracted concentration-dependently in response to Ang II. The concentration-response curve (human jejunum, EC(50): 1.5 +/- 0.8 x 10(-8) M) was shifted to the right by losartan (10(-7) M) but was unaffected by PD123319 (10(-7) M). Both AT1R and AT2R were detected in all segments of the rat small intestinal wall musculature, whereas only AT1R was readily detectable in the human samples.


CONCLUSIONS
Ang II elicits contractions of small-intestinal longitudinal muscle preparations from the small intestine of rats and man. The pharmacological pattern and protein expression analyses indicate mediation via the AT1R.
Ewert
S
S
Department of Gastrosurgical Research, Institute of Clinical Sciences, Sahlgrenska Academy, Goteborg University, Gothenburg, Sweden.
Spak
E
E
Olbers
T
T
Johnsson
E
E
Edebo
A
A
Fändriks
L
L
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis; D044139:Receptor, Angiotensin, Type 2 / Q000032:analysis; D013045:Species Specificity
D018674:Adrenergic Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D018680:Cholinergic Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D001285:Atropine; D019808:Losartan; D006145:Guanethidine