Portal hypertensive gastropathy is considered a serinol-induced gastric injury, related to an inability to ous complication observed in patients with cirrhosis mount a defensive gastric hyperemic response to lumiand portal hypertension. 1,2 The pathophysiology of the nal irritants, and associated with an impaired reactivity profound alterations in mucosal defense against injury of the gastric microcirculation to nitric oxide (NO)/cyclic observed in portal hypertension have demonstrated guanosine monophosphate (cGMP)-dependent vasodilathat the increased susceptibility of the gastric mucosa tors. Whether this hyporesponsiveness is in some way to injury was intimately related to vascular abnormalirelated to depressed prostaglandin synthesis by the ties in the gastric microcirculation. [3][4][5] stomach of cirrhotic rats is not clear. The aims of this
The gastric hyperemic response to irritants is a critistudy were to evaluate the role of NO and prostaglandins cal component of mucosal defense. It is responsible for in the regulation of the gastric microcirculation under resting conditions and in response to administration of the buffering of back-diffused acid and dilution and sodium nitroprusside, as well as to investigate the mechremoval of noxious agents that enter the mucosa. 6 An anisms of the hyporesponsiveness of the gastric microincreased susceptibility of the gastric mucosa to ethacirculation to nitrovasodilators. Cirrhosis was induced nol-induced injury in cirrhotic rats is associated with in rats by bile duct ligation, and controls had sham-opera defective hyperemic response. 3 Vasodilators such as ation. N G -nitro-L-arginine-methyl-ester (L-NAME) and nitric oxide and prostaglandins are believed to be the indomethacin administration produced a greater reducmajor mediators involved in the control of the gastric tion in gastric blood flow in cirrhotic rats than controls. microcirculation and mucosal integrity. [6][7][8][9] Exposure of Indomethacin pretreatment almost completely abolished the responsiveness to sodium nitroprusside the gastric mucosa to an irritant results in activation (NaNP) in cirrhotic rats, while not affecting controls. of sensory afferent nerves, leading to the release of Long-term administration of misoprostol to cirrhotic calcitonin gene-related peptide and, in turn, to dilation rats restored to normal the responsiveness to NaNP, of submucosal arterioles through an NO-dependent whereas long-term administration of aspirin to healthy pathway. 10,11 Cirrhotic rats have a normal anatomic rats resulted in a hyporesponsiveness of the gastric midistribution of the afferent nerves; however, applicacrocirculation to NaNP similar to that seen in cirrhotic tion of acid, 20% ethanol, or capsaicin to the mucosa rats. We conclude that there are interactions between was found not to cause an increase in gastric blood NO and prostaglandins in regulating gastric blood flow in both healthy and cirrhotic rats. The hyporespon-flow. In addition, the gastric blood flow response siveness of the gastric microcirculation of cirrhotic rats to exogenous NO/cyclic guanosine monophosphate to a nitrovasodilator may occur as a consequence of pro-(cGMP)-dependent vasodilators is impaired in cirrhotic longed depression of gastric prostaglandin synthesis. rats. 12 Conversely, cirrhotic rats exhibited an increased (HEPATOLOGY 1996;23:123-129.) responsiveness to cyclic adenosine monophosphate (cAMP)-dependent vasodilators, including prostaglandins. 12,13 Gastric prostaglandin E 2 (PGE 2 ) synthesis is significantly depressed in cirrhotic rats and chronic ad-Abbreviations: cGMP, cyclic guanosine monophosphate; cAMP, cyclic adenosine monophosphate; PGE2, prostaglandin E2; PBS, phosphate-buffered sa-ministration of a PGE 1 analog, misoprostol, resulted in line; L-NAME, N G -nitro-L-arginine-methyl-ester; D-NAME, N G -nitro-D-argia normalization of gastric resistance to ethanol-innine-methyl-ester; BP, blood pressure; NaNP, sodium nitroprusside.