Vascular Smooth Muscle Reactivity and Endothelium Derived Relaxing Factor in Experimental Obstructive Jaundice

Abstract

Obstructive jaundice is associated with a predisposition to systemic hypotension and acute renal failure. Altered vascular reactivity may contribute to the development of hypotension. In this experimental study on dogs, alterations in vascular contractile responses to noradrenaline, serotonin and KCl were investigated. Contractile responses to noradrenaline, serotonin,,, KCL and relaxation responses to papaverin and acetylcholine were provoked in isolated femoral arteries of both control dogs and animals with obstructive jaundice. In this situation concentration-response curves of noradrenaline and serotonin were blunted when compared with controls. This blunting disappeared when endothelium was removed. In rings precontracted with phenylephrine, EDRF relaxation responses to acetylcholine were increased significantly as compared to controls: at lower concentrations maximal relaxation response occurred. Contractile responses to KCl and relaxation responses to papaverin did not differ between the groups, endothelium present or removed. These results indicate that obstructive jaundice induces a decrease in vascular contractile responses and an increased EDRF relaxation response. We suggest that an excess in the amount of released EDRF may be one of the causes inducing systemic hypotension in obstructive jaundice.

Effects Of Experimental Obstructive Jaundice On Contractile Responses Of Dog Isolated Blood Vessels: Role Of Endothelium And Duration Of Bile Duct Ligation

“…Many investigators have concentrated on a possible alteration in vascular tone as an explanation for these clinical findings. An increased incidence of acute renal failure in patients with obstructive jaundice and alterations in vascular reactivity to various agents have been suggested, 5,7,12,17–19 but the data concerning the sensitivity of peripheral vasculature to vasoactive amines have been conflicting. 3–8 …”

“…In the present study, the endothelium‐dependent response to ACh was higher in BDL dogs than in control dogs, thus confirming our previous report. 12 Furthermore, the magnitude of the precontraction was similar in preparations from SO and BDL dogs for PE, thus ensuring that any difference in relaxation between any SO and BDL preparations was not due to differences in the degree of precontraction. In the present study, the relaxation responses to papaverine were similar between the two groups.…”

“…These modulations contribute to changes in vascular responsiveness caused by some diseases. 9–12 Endothelium‐derived relaxing factor has been identified as nitric oxide (NO). 13 Nitric oxide migrates from the endothelium and activates cytosolic guanylyl cyclase of the nearby vascular smooth muscle; this activation accelerates conversion of GTP to cGMP, with cGMP leading, in turn, to vascular smooth muscle relaxation and its accompanying vasodilation.…”

Bile acids and cardiovascular function in cirrhosis

“…Incremental doses of BAs induced vasorelaxation irrespective of blocking agents or denudement of the endothelium showing that the action is probably mediated through inhibition of calcium entry through membranary channels. This is highly influenced by the type of bile acid and indeed it seems that hydrophobic and lypophilic BAs are more likely to induce vasorelaxation . The authors speculated on the mechanism by which bile acids accomplish this effect and concluded that it must be through direct interaction with components of the cellular membrane.…”

“…This is highly influenced by the type of bile acid and indeed it seems that hydrophobic and lypophilic BAs are more likely to induce vasorelaxation. 73 The authors speculated on the mechanism by which bile acids accomplish this effect and concluded that it must be through direct interaction with components of the cellular membrane.…”