The measurement of dog gastric mucosal blood flow by radioactive aniline clearance compared with amidopyrine clearance

1. Methods for the estimation of radioactive aniline in body fluids are described. The recovery of aniline added to blood, plasma and gastric juice was over 90% of the recovery from saline. 2. In the doses used aniline caused methaemoglobinaemia of 5-11% of total haemoglobin. No other effect was detected. Gastric secretion was also unaffected. 3. Aniline clearance increased in parallel with acid secretion from Heidenhain pouches in conscious dogs and in anaesthetized dogs. In conscious dogs the ratio of aniline clearance to acid secretion was significantly higher for histamine stimulation than for pentagastrin stimulation. 4. Aniline and amidopyrine clearances were compared simultaneously in the same dogs. Aniline clearance was about 80% of amidopyrine clearance. 5. The proportion of aniline bound to plasma proteins was measured by two methods and found to be 25%. When aniline clearance was corrected for plasma binding, aniline and amidopyrine clearances were equal

Effects of aspirin-like drugs on canine gastric mucosal blood flow and acid secretion.

1. The effects of aspirin, paracetamol and benorylate were studied on gastric mucosal blood flow (MBF) and acid secretion in canine denervated gastric pouches. 2. Aspirin 20 mM in the unstimulated pouch had no effect; pentagastrin-stimulated acid output, but not MBF, was reduced. Aspirin buffered to pH 6 was ineffective. 3. Aspirin 3-50 mg/kg reaching the pentagastrin-stimulated pouch through the blood, increased acid secretion and MBF, but the MBF:secretion ratio was variably affected. 4. Paracetamol (10 or 20 mg/kg i.v., or 20 mM in the pouch) or benorylate (280 mg/kg orally) mainly had little effect. 5. Circular muscle strips from dog arteries were contracted by prostaglandins E2, F1alpha or F2alpha, and often slightly by indomethacine, but prostaglandin E1 produced variable effects. 6. These results do not favour the view that aspirin causes gastric bleeding in dogs by breakdown of blood vessels due to ischaemia following mucosal vasoconstriction

The effects of isoprenaline and noradrenaline on pentagastrin-stimulated gastric acid secretion and mucosal blood flow in the dog

1. Isoprenaline (0·02 to 2·0 μg kg(-1) min(-1)) inhibited gastric secretion in response to pentagastrin in both conscious and anaesthetized dogs and in response to feeding in conscious dogs. 2. The inhibition was unaffected during cardiac β-adrenoceptor blockade by propranolol. 3. The inhibition was not due to decreased mucosal blood flow. 4. This effect of isoprenaline is different from its effect on histamine-induced gastric secretion. 5. Noradrenaline (0·05-2·0 μg kg(-1) min(-1)) also decreased gastric secretion but it was less effective than isoprenaline. 6. The mechanism of action of noradrenaline is probably a decrease in mucosal blood flow

Gastric juice electrolyte secretion in conscious dogs with gastric fistulae and its modification by FPL 52694, a mast cell stabilizing agent.

Studies have been made of the electrolyte output in the gastric juice of conscious dogs equipped with gastric fistulae during stimulation by intravenous infusion of either pentagastrin (2 micrograms kg-1 h-1), histamine (30 micrograms kg-1 h-1) or insulin (0.1 u kg-1 h-1). The mast cell stabilizing agent, FPL 52694 (4.35 mg ml-1) was instilled into the stomach for 30 min and caused a marked reduction of H+ output, H+ concentration and osmotic strength of the juice during stimulation with pentagastrin, histamine, or insulin. There was also a marked increase in the rate of Na+ output into the juice. When pentagastrin-stimulated acid secretion was inhibited by cimetidine (4 mumol kg-1 i.v.) acid output was reduced but there were no sustained changes in ion concentrations, osmolarity or Na+ output of the type seen following inhibition with FPL 52694. It is concluded that FPL 52694 may have a dual mode of action in this preparation; a direct reduction of the output of hydrochloric acid and a smaller effect to increase gastric NaHCO3 output leading to a post-secretory neutralization of the juice

Inhibition of gastric acid secretion in the conscious dog by the mast-cell stabilizing agent, FPL 52694.

The effects of the mast-cell stabilizing agent, FPL 52694, on gastric acid secretion in conscious dogs with gastric fistulae have been studied. FPL 52694 (5 or 10 mg kg-1 h-1) given intravenously during a plateau response to pentagastrin stimulation (2 micrograms kg-1 h-1) caused a maximum inhibition of acid output of about 50% but had no significant effect on volume output so that the [H+] in the juice was markedly reduced. The ratio of mucosal blood flow/acid output (Ra) was increased in the presence of FPL 52694. There was no maintained reduction of [H+] when inhibition was due to cimetidine (4 mumol kg-1, i.v.). Instillation of FPL 52694 (4.35 mg ml-1) directly into the stomach via the fistula for 30 min also resulted in an inhibition of acid output and reduction of [H+] during both pentagastrin-(2 micrograms kg-1 h-1) and histamine-stimulated (30 micrograms kg-1 h-1) secretion. Inhibition of pentagastrin-stimulated acid output by intragastric administration of FPL 52694 was much greater than the maximum effect seen following intravenous infusion. The results are discussed in relation to the possible mode of action of FPL 52694. It is concluded that FPL 52694 is active orally and has a novel action on acid secretion which may include stimulation of gastric bicarbonate secretion