Alteration in vascular reactivity in isolated aortic rings from portal vein—constricted rats

Abstract

It has been suggested that increased production of nitric oxide by an inducible nitric oxide synthase isoenzyme is important in the pathogenesis of the vascular abnormalities seen in human beings and animals with portal hypertension. We investigated this hypothesis by studying the in vitro vascular reactivity of isolated aortic rings from portal vein-constricted and sham-operated rats. Aortic rings from portal vein-constricted rats exhibited significantly impaired contractility to phenylephrine and potassium chloride compared with control rats. Preincubation with the nitric oxide synthase inhibitor nitro-L-arginine methyl ester significantly increased contractility to phenylephrine and potassium chloride in both portal-hypertensive and control tissues, with greater effect in the portal-hypertensive rings. Despite nitro-L-arginine methyl ester, maximal contractions were still significantly smaller in the portal-hypertensive tissues. Vascular relaxation evoked by acetylcholine, but not by the endothelium-independent vasodilator glyceryl trinitrate, was significantly impaired in the portal-hypertensive group. Our results demonstrate significant impairment in vascular function in aortic rings in this model of portal hypertension. The addition of a nitric oxide synthase inhibitor partly corrected these changes, suggesting that although nitric oxide is likely an important mediator, other factors may also be involved in the pathogenesis of these alterations in vascular function.

Anatomical differences in responsiveness to vasoconstrictors in the mesenteric veins from normal and portal hypertensive rats

“…Portal hypertension is associated with marked alterations in vascular reactivity (Grozsmann and Atterbury 1982;Bosch et al 1992Bosch et al , 1994) and most experimental studies have reported diminution of systemic and mesenteric arterial responses to endogenous vasoconstrictors, both in vivo (Sitzmann et al 1990;Sieber et al 1992a;Joh et al 1993;Wu and Benoit 1994) and in vitro (Sieber et al 1992b;Claria et al 1994;Karatapanis et al 1994;Liao et al 1994). Much less attention has been paid to the disturbances in the vascular reactivity of the portal-mesenteric venous system.…”

“…Arterial contractile responses, both in vivo and in vitro, are generally decreased in portal hypertension (Kiel et al 1985;Sieber et al 1992a, b;Bosch et al 1992Bosch et al , 1994Claria et al 1994;Karatapanis et al 1994) a fact that has been attributed to an excessive release of endogenous relaxant substances such as glucagon and other vasodilatory peptides (Benoit et al 1984(Benoit et al , 1986Pizcueta et al 1990;Mesh et al 1991) nitric oxide (Pizcueta et al 1991;Sieber et al 1992a, b) as well as prostacyclin (Sitzmann et al 1989;Wu et al 1993). However, these observations contrast with results in isolated longitudinal smooth muscle of mesenteric vein showing that portal hypertension elicits increased contractile responses to two different vasoconstrictors, i.e.…”

Role of cyclic guanosine monophosphate and K+channels as mediators of the mesenteric vascular hyporesponsiveness in portal hypertensive rats

“…13,15 Other studies have also suggested that NO is only partly involved in the defective mesenteric pressor response. 11,17,18 We hypothesized that other endothelium-derived vasodilating factors, with the ability to counteract the pressor effect of endogenous or exogenous vasoconstrictors, could have a role in the mediation of the hyporesponsiveness to vasoconstrictors in liver diseases. Among them, it is known that activation of potassium channels hyperpolarizes smooth muscle and produces vasodilation.…”

Nitric Oxide and Hemodynamic Impairment

“…The endothelium produces at least two substances that are aortic rings demonstrated increased relaxation to the vasodilator acetylcholine (endothelial agonist) compared to known to contribute to the development of systemic and splanchnic vasodilatation in portal hypertension: nitric sham controls. This increased response to acetylcholine was partly reversed with L-NAME [4]. oxide (NO) and prostaglandins [1].…”