Adrenergic Response of Splanchnic Arteries from Cirrhotic Patients: Role of Nitric Oxide, Prostanoids, and Reactive Oxygen Species

Abstract

Peripheral and splanchnic vasodilatation in cirrhotic patients has been related to hyporesponsiveness to vasoconstrictors, but studies to examine the vascular adrenergic response provide contradictory results. Hepatic arteries from cirrhotic patients undergoing liver transplantation and mesenteric arteries from liver donors were obtained. Segments 3 mm long from these arteries were mounted in organ baths for testing isometric adrenergic response. The concentration-dependent contraction to noradrenaline (10(-8) to 10(-4) M) was similar in hepatic and mesenteric arteries, and prazosin (alpha 1-adrenergic antagonist, 10(-6) M), but not yohimbine (alpha 2-adrenergic antagonist, 10(-6) M), produced a rightward parallel displacement of this contraction in both types of arteries. Phenylephrine (alpha 1-adrenergic agonist, 10(-8) to 10(-4) M) and clonidine (alpha 2-adrenergic agonist, 10(-8) to 10(-4) M) also produced concentration-dependent contractions that were comparable in hepatic and mesenteric arteries. The inhibitor of cyclooxygenase meclofenamate (10(-5) M), but not the inhibitor of nitric oxide synthesis N(w)-nitro-l-arginine methyl ester (l-NAME, 10(-4) M), potentiated the response to noradrenaline in hepatic arteries; neither inhibitor affected the response to noradrenaline in mesenteric arteries. Diphenyleneiodonium (DPI; 5 x 10(-6) M), but neither catalase (1000 U/ml) nor tiron (10(-4) M), decreased the maximal contraction for noradrenaline similarly in hepatic and mesenteric arteries. Therefore, it is suggested that, in splanchnic arteries from cirrhotic patients, the adrenergic response and the relative contribution of alpha 1- and alpha 2-adrenoceptors in this response is preserved, and prostanoids, but not nitric oxide, may blunt that response. Products dependent on NAD(P)H oxidase might contribute to the adrenergic response in splanchnic arteries from control and cirrhotic patients.

Iloprost, Prostaglandin E1, and Papaverine Relax Human Mesenteric Arteries With Similar Potency

“…There were significant differences regarding the logEC 50 values spanning three orders of magnitude indicating large differences in mesenteric artery sensitivity to the contractile effects of AVP, ET-1 and NE which is in agreement with the available literature (24)(25)(26)(27). In studies reporting poor phenylephrine responsiveness of human mesenteric arteries (28) and in the present study, patients were older than in studies reporting maximum vasoconstrictor effects close to or exceeding high potassium-induced rises in wall tension (25,29). Our data suggest that 2 -adrenoceptors mediate to a large extent the NEinduced constrictions in human mesenteric arteries.…”

“…There were significant differences regarding the logEC 50 values spanning three orders of magnitude indicating large differences in mesenteric artery sensitivity to the contractile effects of AVP, ET-1 and NE which is in agreement with the available literature (24)(25)(26)(27). We found that the three physiological vasoconstrictors tested induced similar maximum increases in wall tension.…”

Comparison of Adrenergic and Purinergic Receptor Contributions to Vasomotor Responses in Mesenteric Arteries of C57BL/6J Mice and Wistar Rats

“…Similar to our results in mice and rats, these data support a role for α 1 AR in modulating vasoconstriction to adrenergic activation. Mesenteric arteries from patients with cirrhotic liver disease displayed robust vasoconstriction to NE that could be attenuated by prazosin, but not yohimbine, an α 2 antagonist [75]. Although these data are in line with our observation in rats (α 1A AR activity without much evidence for α 2 AR activation), the study was lacking a nondiseased control group for comparison.…”

A comparison of intra‐operative blood loss and acid–base balance between vasopressor and inotrope strategy during living donor liver transplantation: a randomised, controlled study

“…Major surgery in patients who already have a tendency towards vasodilatation, such as cirrhotic patients undergoing liver transplantation, is associated with a frequent requirement for intra‐operative administration of either inotropes or vasopressors [5, 13, 14]. Although a previous study has suggested that the response to vasoconstrictors may be blunted in cirrhosis [15], other more recent studies have disputed this [16, 17]. Noradrenaline and phenylephrine are the most commonly used vasopressors in modern clinical practice.…”

“…Although there are few reports in the literature, phenylephrine is also frequently used during liver transplantation. It has been shown to cause vasoconstriction in mesenteric and hepatic arteries in cirrhotic patients [17].…”