Effect of angiotensin II and telmisartan, an angiotensin(1) receptor antagonist, on rat gastric mucosal blood flow

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 haemod ynamics and the hyperaemic response to acid back-diffusion of ATII and the angiotensin ATI receptor antagonist, telmisartan, were examined in normal r ats and in animals subjected to haemorrhage, Methods: Gastric mucosal blood now 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-dep endent 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 antago nized by intravenous injection of telmisartan (1-10 mg/kg) which per se cau sed hypotension and dilated the gastric mucosal vasculature, but did not mo dify the gastric mucosal hyperaemia evoked by acid back-diffusion. Hypotens ion induced by haemorrhage (1.3 mt blood per 100 g body weight) failed to a lter 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 endoge nous ATII contributes to the homeostatic regulation of gastric vascular ton e but does not compromise the ability of the gastric microvasculature to re act to influxing acid. These results negate the concept that ATII contribut es to the gastric vascular perturbances in haemorrhagic shock.