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Effect of angiotensin II and telmisartan, an angiotensin 1 receptor antagonist, on rat gastric mucosal blood flow
Author(s) -
Ákos Heinemann,
Sattler,
Jocic,
Wienen,
Peter Holzer
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00496.x
Subject(s) - telmisartan , medicine , angiotensin ii receptor antagonist , antagonist , angiotensin ii , angiotensin ii receptor type 1 , angiotensin receptor , receptor antagonist , pharmacology , endocrinology , receptor , blood pressure
Background: Angiotensin II (ATII) has been suggested to contribute to shock‐induced dysfunction of the gastric circulation. Aim: To substantiate this conjecture, the effects on gastric mucosal haemodynamics and the hyperaemic response to acid back‐diffusion of ATII and the angiotensin AT 1 receptor antagonist, telmisartan, were examined in normal rats and in animals subjected to haemorrhage. Methods: Gastric mucosal blood flow in phenobarbital‐anaesthetized rats was recorded with the hydrogen clearance technique, and acid back‐diffusion was induced by perfusing the stomach with ethanol (25%) in HCl (0.05 M ). Results: Intravenous infusion of ATII (0.3–10 nmol/min/kg) led to dose‐dependent hypertension and a reduction of blood flow and vascular conductance in the gastric mucosa. The gastric hyperaemia caused by acid back‐diffusion was attenuated by ATII (1 nmol/min/kg). These effects of ATII were antagonized by intravenous injection of telmisartan (1–10 mg/kg) which per se caused hypotension and dilated the gastric mucosal vasculature, but did not modify the gastric mucosal hyperaemia evoked by acid back‐diffusion. Hypotension induced by haemorrhage (1.3 mL blood per 100 g body weight) failed to alter the hyperaemia due to acid back‐diffusion, but caused gastric mucosal vasoconstriction, an effect that was left unaffected by telmisartan. Conclusions: ATII constricts the rat gastric microvasculature via an action involving AT 1 receptors. The effects of telmisartan indicate that endogenous ATII contributes to the homeostatic regulation of gastric vascular tone but does not compromise the ability of the gastric microvasculature to react to influxing acid. These results negate the concept that ATII contributes to the␣gastric vascular perturbances in haemorrhagic shock.