Role of EDRF in splanchnic blood flow of normal and chronic portal hypertensive rats

Abstract

The role of endogenous endothelium-derived relaxing factor (EDRF) in splanchnic blood flow was assessed in normal and portal vein-stenosed rats (PSRs). Specific and maximal inhibition of EDRF was achieved by intravenous administration of NG-nitro-L-arginine (L-NOARG) as a 1.75 mumol/kg bolus, followed by constant infusion of 1.75 mumol/kg for 20 min. Pretreatment with L-arginine (175 mumol/kg iv) completely blocked both hypertension and the reduction in blood flow induced by L-NOARG. Pretreatment with D-arginine (175 mumol/kg iv) and prazosin (500 micrograms/kg iv) did not attenuate the pressor effect of L-NOARG. These results indicate that L-NOARG selectively blocks EDRF. The blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats was 81.1 +/- 8.7, 199.1 +/- 21.9, 153.3 +/- 20.0, 68.6 +/- 10.6, 79.4 +/- 11.8, and 59.3 +/- 7.8 ml.min-1.100 g-1, respectively, and in PSRs was 141.4 +/- 10.8, 244.0 +/- 10.4, 208.3 +/- 9.8, 126.8 +/- 13.0, 166.9 +/- 16.5, and 94.8 +/- 4.7 ml.min-1.100 g-1, respectively. Blood flow was measured using the radioactive microsphere method. L-NOARG significantly reduced blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats by 47, 44, 48, 55, 40, and 41%, respectively, and in PSRs by 30, 27, 36, 33, 28, and 23%, respectively. The magnitude of blood flow reduction in PSRs was lower than in normal rats. These results indicate that EDRF plays an important role in control of the splanchnic circulation, but its effect on the hyperdynamic circulation observed in PSRs is insignificant.

l‐NAME, nitric oxide and jejunal motility, blood flow and oxygen uptake in dogs

“…The utilization of these analogues also has a potential problem in the elucidation of the role of NO in the gastrointestinal tract. Previous studies, which utilized NO synthesis inhibitors showed that these inhibitors not only decrease gastrointestinal blood flow (Gardiner et al, 1990a,b;Iwata et al, 1992;Pique et al, 1992), but also increase gut motility (Dalziel et al, 1991;Allesher et al, 1992;Calignano et al, 1992;Knudsen et al, 1992;Ward et al, 1992;Yamato et al, 1992). None of these studies, however, reported the influence of the increased motility on blood flow.…”

“…Furthermore, administration of nitroglycerin or other nitrate increases blood flow to the small intestine and other organs via generation of NO (Frohlich et al, 1965;Ignarro, 1989). Therefore it has been suggested that basal release of NO plays a physiological role in regulation of the skeletal muscle, renal, splanchnic, coronary and internal carotid blood flows, and systemic arterial blood pressure (Whittle et al, 1989;Gardiner et al, 1990a,b;Rees et al, 1990; Iwata et al, 1992;Jones & Brody, 1992;Pique et al, 1992). In the gastrointestinal tract, NO has also been suggested to play a role in regulation of gastrointestinal motility, particularly in the neurally mediated relaxations of the ' Author for correspondence.…”

Enhanced cyclooxygenase-1 expression within the superior mesenteric artery of portal hypertensive rats: Role in the hyperdynamic circulation

“…9,27 Whereas enhanced NO production may be a major modulator of the altered vascular response in PHT, other vasodilator substances may also be involved in as much as acute or chronic blockade of NOS activity fails to completely reverse the hyperdynamic circulation. 13,14 We now report on the regulation of Cox-I expression within the hyperemic vasculature of PHT rats and its role in contributing to the elevated superior mesenteric blood flow (splanchnic blood flow). The temporal changes in splanchnic hemodynamics following ligation in rats receiving 0.9% saline are very similar to that reported previously by Sikuler et al 28 Qsma is decreased in PHT animals on day 2 due to the acute obstruction to portal inflow from the portal vein ligation.…”

“…11,12 While the enhanced NO production may be a major modulator of the altered vascular response in PHT, other vasodilator substances may also be involved inasmuch as acute blockade of NOS activity fails to completely reverse the hyperdynamic circulation. 13,14 The production of prostacyclin (PGI 2 ) is increased in experimental PHT and in patients with chronic liver disease. [15][16][17] Moreover, indomethacin administration attenuates the hyperdynamic circulation and vascular hyporesponsiveness to vasoconstrictors typical of PHT.…”

Vasopressin reverses mesenteric hyperemia and vasoconstrictor hyporesponsiveness in anesthetized portal hypertensive rats

“…4,5 Although there is growing evidence for the ''NO hypothesis,'' 15,30,[33][34][35][36] controversy exists whether additional NO-independent mechanisms might be involved in the hemodynamic derangements in portal hypertension. For example, some groups reported complete reversal of the splanchnic hyperemia 37 and in vitro hyporeactivity, 27,31,38,39 whereas others observed no or only partial correction of the splanchnic vasodilation [40][41][42][43] and the blunted responsiveness to vasoconstrictors in vitro 10,[44][45][46][47] after NO inhibition. As to what extent these conflicting data on the role of NO are caused by methodological differences (e.g., varying degrees of portal stenosis and portal-systemic shunting) warrants further investigation.…”