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Cardiac plasma membrane physical properties and beta-adrenergic receptor function are unaltered in
1Liver Unit, University of Calgary, Canada.
Insights
Portal hypertension in rats does not alter cardiac membrane properties or beta-adrenergic receptor function. This suggests cirrhosis-related heart dysfunction stems from cirrhosis itself, not portal hypertension alone.
Area of Science:
- Cardiovascular Physiology
- Hepatology
- Membrane Biophysics
Background:
- Cirrhosis impairs cardiac contractility, potentially due to altered cardiac plasma membrane properties affecting beta-adrenergic receptor function.
- The specific role of portal hypertension versus cirrhosis in these cardiac changes remains unclear.
Purpose of the Study:
- To investigate cardiomyocyte plasma membrane physical properties, lipid composition, and beta-adrenergic receptor function in a rat model of prehepatic portal hypertension without cirrhosis.
- To determine if portal hypertension itself, independent of cirrhosis, affects cardiac membrane function.
Main Methods:
- Induction of portal hypertension via graded portal vein stenosis in rats, with sham-operated controls.
- Assessment of cardiac sarcolemmal plasma membrane fluidity using fluorescent polarization.
- Measurement of beta-adrenergic receptor density and binding affinity using radioligand assays.
- Quantification of isoproterenol-stimulated adenylyl cyclase activity.
Main Results:
- No significant differences were observed in membrane fluidity (static and dynamic components) between portal-hypertensive and control rats.
- Cardiac membrane cholesterol, phospholipid content, and cholesterol/phospholipid ratios were comparable between groups.
- Beta-adrenergic receptor density, binding affinity, and isoproterenol-stimulated adenylyl cyclase activity remained unimpaired in portal-hypertensive rats.
Conclusions:
- Cardiac plasma membrane physical properties and beta-adrenergic receptor function are not impaired in rats with portal hypertension.
- These findings suggest that the cardiomyopathy associated with cirrhosis is not caused by portal hypertension per se.
- The cardiac dysfunction in cirrhosis likely arises from factors other than portal hypertension.
Abstract:
We have previously demonstrated that impairment of cardiac contractility in a rat model of cirrhosis may be secondary to altered cardiac plasma membrane physical properties affecting beta-adrenergic receptor function. It is unclear whether this is caused by the cirrhosis or by the portal hypertension in this model, so we studied cardiomyocyte plasma membrane physical properties, lipid composition, and beta-adrenergic receptor function in a rat model of prehepatic portal hypertension without cirrhosis. Portal hypertension was induced by graded portal vein stenosis, whereas controls had a sham operation. Cardiac sarcolemmal plasma membrane physical properties were studied by fluorescent polarization methods using diphenylhexatriene and a series of anthroyloxy-stearic acids to estimate, respectively, the static and dynamic components of membrane fluidity. beta-Adrenergic receptor density and binding affinity were measured using 3H-dihydroalprenolol as a radioligand. Isoproterenol-stimulated adenylyl cyclase activity was measured by radioimmunoassay. Neither the static nor the dynamic components of membrane fluidity were significantly different in portal-hypertensive rats compared with the controls. The membrane cholesterol, phospholipid content, and the cholesterol/phospholipid ratio did not differ between the two groups. beta-Adrenergic receptor density and binding affinity in the portal-hypertensive rats (respectively, 1.65 +/- 0.06 pmol/mg protein and 6.78 +/- 0.80 nmol/L) were not different from controls (1.76 +/- 0.17 pmol/mg protein and 7.25 +/- 1.48 nmol/L). Isoproterenol-stimulated adenylyl cyclase activity in membranes from portal-hypertensive rats did not significantly differ from controls. We conclude that cardiac plasma membrane physical properties and beta-adrenoceptor function in portal hypertensive rats remains unimpaired, suggesting that the cardiomyopathy of cirrhosis is not caused by portal hypertension per se.