Hiroshi Kohei

Endothelium-dependent increases in rat gastric mucosal hemodynamics induced by acetylcholine and vagal stimulation

The role of vascular endothelial cells in the vagal control of hemodynamics was studied in rat gastric mucosa. Vagal stimulation and intra-arterial administration of acetylcholine and of papaverine increased hemoglobin (Hb) and oxygen saturation of hemoglobin (SO2) in the gastric mucosa. The increases induced by vagal stimulation were reduced but not abolished by atropine. The responses to acetylcholine and vagal stimulation were reduced by quinacrine, p-bromophenacyl bromide and nordihydroguaiaretic acid, while indomethacin had no effect. Intra-arterial infusion of collagenase removed the endothelial cells from submucosal vasculatures and depressed the increase in mucosal hemodynamics in response to acetylcholine and vagal stimulation. The response to papaverine was not depressed in rats treated with quinacrine or collagenase. These results suggest that the increase in gastric mucosal blood flow induced by acetylcholine or vagal stimulation is mediated by the endothelium-derived relaxing factor.

Roles of Gastric Acid Secretion and Motility in Gastric Mucosal Lesion Formation Induced by Water-Immersion Stress in Rats

The roles of gastric acid and motility in gastric mucosal lesion formation induced by water-immersion stress were studied pharmacologically in rats. Gastric acid secretion and motility increased markedly during water-immersion, and mucosal lesions were formed. Cimetidine inhibited the increase in gastric acid secretion, but papaverine inhibited the increases in both acid secretion and motility. Both agents prevented the formation of mucosal lesions. In acid perfused rats, the increase in motility and lesion formation induced by water-immersion stress were prevented by papaverine, but not by cimetidine. These results suggest that the increases in both acid secretion and motility play important roles in the formation of mucosal lesions induced by water-immersion stress in rats.

Gastric mucosal protective action of endothelium-derived relaxing factor.

The change in the endothelial function by the application of 0.6 N HCl and the effects of endothelium-derived relaxing factor (EDRF) inhibitors and nitrites on HCl-induced lesions were studied to clarify the effect of EDRF on gastric lesions in rats. The EDRF-induced increase in the gastric mucosal hemodynamics induced by vagal stimulation or intra-arterial administration of acetylcholine was inhibited by the EDRF inhibitors or removal of endothelial cells. Topical application of 0.6 N HCl on the exposed gastric mucosa abolished the response of the mucosal hemodynamics to acetylcholine or vagal stimulation. Gastric lesions induced by 0.45 N HCl were enhanced by EDRF inhibitors or removal of endothelial cells from gastric submucosal arterioles.

Enhancement of contractile responses to partial α-adrenoceptor agonists during warming in rat aorta

SummaryWe examined the effects of warming on the contractile responses to full and partial α-adrenoceptor agonists in rat aorta. The contractions elicited by norepinephrine and methoxamine were not affected during warming (40°C, 42°C), whereas those induced by clonidine and St 587 were significantly enhanced. KCl-induced contractions of rat aorta were not affected by warming. The dissociation constants of clonidine and St 587 at 40°C were not different from those at 37°C. At 40°C, the receptor occupancy-contractile response curve of clonidine was a hyperbolic curve similar to that of methoxamine at 37°C, although at 37°C the curve was almost linear. The responses of St 587 at both 37°C and 40°C were related inversely hyperbolic to the receptor occupancy, but the receptor occupancy-contractile response curve was shifted to the left and upward during warming. Clonidine and St 587 elicited equal responses at lower fractional occupancies at 40°C than at 37°C. The relative efficacies of clonidine and St 587 to methoxamine were significantly augmented during warming. It is suggested that the contractile responses to partial α-adrenoceptor agonists in rat aorta are enhanced during warming, and that this effect is related to the intrinsic efficacy of the agonists rather than to any function of their relative selectivity for α1- or α2-adrenoceptors. Such enhancement is due to augmentation of the efficacy rather than to augmentation of the affinity of the agonists.

Studies on the formation of cyclohexylamine and n-methylcyclohexylamine from bromhexine in animals and man, and simultaneous determination of cyclohexylamine and n-methylcyclohexylamine by gas chromatography

In order to detect cyclohexylamine and N-methylcyclohexylamine simultaneously in urine, a gas chromatographic method was developed in which Chromosorb 103 (porous polymer) was found to be suitable as the column packing. The detection limits were 0.1 mug/ml of cyclohexylamine and 0.4 mug/ml of N-methylcyclohexylamine in urine. In tests on animals administered bromhexine, which contains N-methylcyclohexylamine as part of its side-chain, neither cyclohexylamine nor N-methylcyclohexylamine was detected in the urine.