Effects of Prostacyclin Inhibition on Splanchnic Hyposensitivity to Glypressin in a Hemorrhage-Transfused Rat Model of Portal Hypertension

Abstract

The improvement of splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension by the administration of indomethacin suggests that PGI2 has in the development of this hyposensitivity.

Inhibition of glucagon improves splanchnic hyporesponse to terlipressin in cirrhotic rats with blood retention in the gastric lumen

“…However, the magnitude of changes in mean arterial pressure and cardiac index following terlipressin administration were similar. These results suggest that the accumulation of blood in stomach, similar to that occurred in acute hemorrhage, was associated with a selective splanchnic hyporesponse to terlipressin in cirrhotic rats [11,12,42]. However, it is also possible that the portal pressure and SMA blood flow were already elevated in cirrhotic rats with portal hypertension.…”

“…However, the simultaneously infusion of glucagon antiserum or octreotide in blood gavaged-cirrhotic rats did not completely correct the splanchnic hyporesponse. It is possible that other factors (such as prostacyclin and nitric oxide) also contribute to the splanchnic hyporesponse to terlipressin in cirrhotic rats with portal hypertension [11,12]. In this study, both the infusion of glucagon antiserum and octreotide were proved to inhibit the increasing plasma glucagon concentration and the corresponding elevation of portal pressure in blood gavage-cirrhotic rats.…”

“…Terlipressin was administered by intravenous injection at a dose of 0.07 mg/kg as previously [11,12]. Octreotide was administered by intravenous injection at a dose of 8 mg/kg as previously [35,36].…”

“…However, previous studies have shown that the portal hypotensive effects of these drugs are less effective during acute variceal hemorrhage than under stable conditions [5][6][7]. The mechanisms of the splanchnic hyporesponse to vasopressin during hemorrage are poorly understood [8][9][10], but may involve increased synthesis of nitric oxide and prostacyclin [11,12].…”

Inhibition of prostacyclin by indomethacin ameliorates the splanchnic hyposensitivity to glypressin in haemorrhage‐transfused common bile duct‐ligated rats

“…In addition, the modulator role of NO and PGI 2 in the vascular actions of arginine vasopressin has been suggested [21,22]. This may be the reason why the blockade of NO or PGI 2 synthesis in bleeding PVL rats could alleviate the hyposensitivity to glypressin [6,23], suggesting the blunted vascular activity plays a key role in the pathophysiology of glypressin hyposensitivity.…”