Is the hypotension of cirrhosis a GABA-mediated process?

Abstract

Systolic and diastolic blood pressures were recorded in 176 ambulant patients with chronic liver disease, including 36 patients with compensated cirrhosis (Group I), 119 patients with noncirrhotic chronic liver disease (Group II) and 21 patients with benign structural or functional liver disease (Group III). Group I patients had significantly lower systolic (113.0 +/- 2.2 mm Hg, mean +/- S.E.) and diastolic (65.3 +/- 1.7 mm Hg) pressures than Group II patients (125.8 +/- 3.5 and 76.6 +/- 1.5 mm Hg, respectively (p less than 0.0001) or Group III patients (125.1 +/- 3.4 and 77.5 +/- 2.4 mm Hg, respectively) (p less than 0.0001). Serum levels of GABA, a potent amino acid neurotransmitter with known vasodilatory effects in vitro, were higher in Group I patients (1.12 +/- 0.26 microM, mean +/- S.E.) than in Group II patients (0.41 +/- 0.05 microM) (p less than 0.005) or Group III patients (0.34 +/- 0.03 mM) (p less than 0.05). A constant infusion of GABA into the systemic circulation of six adult dogs, at rates required to achieve serum GABA levels within one order of magnitude of those observed in humans with cirrhosis, resulted in a 17.0 +/- 4.3 mm Hg decrease in systolic pressure (p less than 0.05) and a 10.8 +/- 3.7 mm Hg decrease in diastolic pressure (p less than 0.05). Control amino acids were not vasoactive. The results of this study suggest that, in addition to other vasoactive compounds, a GABA-mediated process might contribute to the hypotension observed in patients with compensated cirrhosis.

Prevalence and Prediction of Coronary Artery Disease in Patients With Liver Cirrhosis

“…5,6 This might in principle be supported by the favorable cardiovascular risk profiles of cirrhosis per se in terms of the hemostatic defects such as impaired coagulation, thrombocytopenia, and platelet dysfunction, low blood pressure and cholesterol levels, and high levels of circulating estrogens, as well, seen in previous and, in part, also in the current series. 7,35,38 However, because we did not find these factors to be significantly prognostic, this argument may be fallacious. On the other hand, some recent studies have suggested that cirrhotic conditions promote CAD because moderate to severe coronary stenotic disorders seemed to be relatively prevalent in LT candidates, accounting for up to 27% of the candidates.…”

“…We found that the prevalence of obstructive CAD among cirrhotic patients without symptoms or histories of heart attack did not differ significantly from that among a propensity score-matched nonhepatic control group. In a multivariable analysis, the prevalence was completely independent of clinical parameters that can be affected by the severity of liver cirrhosis, such as hyperlipidemia, arterial hypertension, diabetes mellitus, and BMI [32][33][34][35][36] although the cirrhotic cases were at higher risk of nonobstructive lesions, which have a more favorable course. 25,[27][28][29][30] The prevalence of obstructive disease in both sets was ≈8%, and the traditional clinical predictors such as age, sex, hypertension, and diabetes mellitus contributed substantially to coronary narrowing in the hepatic patients.…”

Mechanisms of hypertension during and after orthotopic liver transplantation in children

“…28,29 Indeed, the physiologic adaptations to chronic liver failure will be markedly altered by the posttransplant circulatory environment. 37,38 Vasopressin is released in response to dehydration, salt administration, hypotension, and surgical stress. [39][40][41][42] Atrial distension, not increased atrial pressure, and acute but not chronic salt loading lead to increased circulating ANF.…”

Cardiac and vascular changes in cirrhosis: Pathogenic mechanisms

“…Some studies suggest the possible involvement of other humoral vasodilators, but a definitive pathogenic role for any of these substances remains elusive. This list includes: glucagons [37] , prostaglandins [38] , GABA [39] , VIP [40] , bile acids [41] , endotoxin, histamine [42] and adenosine [43] .…”