Role of prostaglandins and nitric oxide in gastrointestinal hyperemia of diabetic rats

Abstract

The aim of the study was to characterize the gastric and mesenteric vascular changes induced by diabetes and the implication of endothelial [nitric oxide (NO) and prostaglandins] and humoral (glucagon) factors in such changes. Diabetes was induced in rats by a single streptozotocin injection. Four weeks later, gastric mucosa, left gastric artery, and superior mesenteric artery blood flows were measured using hydrogen gas clearance and perivascular ultrasonic flowmeter techniques, respectively, in anesthetized and fasted diabetic and control rats. Blood pressure, hematocrit, blood volume, and blood viscosity were also measured. Left gastric (41 +/- 6 vs. 25 +/- 4 ml.min-1.100 g-1) and superior mesenteric artery blood flows (83 +/- 8 vs. 65 +/- 4 ml.min-1.100 g-1) were significantly higher in diabetic than in control rats. The increased blood flow in the left gastric artery was distributed to a hypertrophic mucosa in diabetic rats; therefore, the blood flow per 100 g tissue in the gastric mucosa was not significantly different in diabetic compared with control rats. Pretreatment with indomethacin reduced both increase gastric and mesenteric flows of the diabetic rats to the same levels as in control rats. NG-nitro-L-arginine methyl ester decreased gastric blood flow in a dose-dependent manner and to a similar extent in diabetic and control rats. In contrast, an increased sensitivity to the higher doses of the NO inhibitor was observed in the mesenteric vascular bed of diabetic rats. Glucagon reduction achieved by somatostatin infusion did not influence either gastric or mesenteric blood flow in diabetic rats. In summary, the present study revealed an increase in gastric and mesenteric arterial blood flows in streptozotocin-induced diabetic rats. The gastrointestinal hyperemia seems to be due, at least in part, to the increased demand of a hypertrophic mucosa and is mediated primarily by endogenous prostaglandins. Increased vascular sensitivity to NO may also contribute to the mesenteric vasodilation.

Increased Susceptibility of Diabetic Rat Gastric Mucosa to Food Deprivation during Cold Stress

“…In our study, diabetic rats had considerably higher NOx plasma levels than their age-matched, healthy littermates which is not surprising, as an almost 100% increase in NOx blood plasma level has been described in rats, 6 weeks after STZ injection [29]. Although the reports of NOS activity in diabetic gastric mucosa are scarce and conflicting [24, 30], we demonstrated an increase of total NOS and iNOS activities in gastric corpus mucosa of starved and cold-stressed diabetic animals, the results being consistent in part with our previous work [31]. Thus, it was not unexpected that NOx output in the gastric juice was augmented in diabetic rats as stress, during which stomach is one of the target organs, stimulates NO release [32].…”

“…Quite to the contrary, other researchers demonstrated an increase in the left gastric and superior mesenteric arterial blood flows, but surprisingly no overall differences in gastric mucosal blood flow between control and diabetic rats. The described discrepancies might depend on whether the measurement outcomes have been expressed per 100 g mucosa [6, 24]. All factors considered, in our opinion the ischemic component could considerably add to the increased susceptibility of diabetic mucosa to damage, as the hyperemic responses following capsaicin application and accompanying H + backdiffusion were markedly diminished in a disease duration dependent manner in STZ-injected rats [25].…”

Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries

“…This is consistent with the enhanced mediation by endogenous prostaglandins of the increased gastric and mesenteric Ž . blood flow observed in diabetic rats Goldin et al, 1996 and with the increases in vasodilator prostanoid release in Ž . diabetic coronary arteries Koltai et al, 1997 .…”

Temporal changes in vascular reactivity in early diabetes mellitus in rats: role of changes in endothelial factors and in phosphodiesterase activity

“…Some investigators suggested a decrease in nitric oxide (NO) activity (1,27), while others proposed an impairment in endothelium-derived hyperpolarizing factor (EDHF) activity (39,42) or in cyclooxygenase activity (4,38) as causes of the significant decrease in endothelium-dependent vasodilatation in diabetic tissues. In contrast, other studies reported an enhanced endothelium-dependent relaxation secondary to increased production of NO (2,26,35) or prostacyclin (2,9,14,18,28).…”

“…Some investigators suggested a decrease in nitric oxide (NO) activity (1, 27), while others proposed an impairment in endothelium-derived hyperpolarizing factor (EDHF) activity (39, 42) or in cyclooxygenase activity (4, 38) as causes of the significant decrease in endothelium-dependent vasodilatation in diabetic tissues. In contrast, other studies reported an enhanced endothelium-dependent relaxation secondary to increased production of NO (2, 26, 35) or prostacyclin (2,9,14,18,28).It is clear that the results of vascular reactivity studies in animal models of diabetes are contradictory, and there is not an entirely satisfactory explanation for the variable responses of diabetic blood vessels to vasoconstrictor and vasodilator drugs. Possible explanations may involve differences in species, duration of diabetes, etiology of diabetes, type of vascular preparation studied, and type of vasoconstrictor or vasodilator used in the various studies, among other factors.…”