Cardiac excitation-contraction coupling in the portal hypertensive rat

Abstract

Basal contractility and responses to β-adrenoceptor activation are compromised in hearts from rats with chronic portal vein stenosis. Here we report the effect of partial ligation of the portal vein on myocardial G protein expression, β-adrenoceptor-G protein coupling, and excitation-contraction coupling (ECC). Contractility (d T/d t) was reduced 30–50% in right and left ventricles, but the rate of relaxation (−d T/d t) was unaffected. Isoproterenol-induced positive inotropism was diminished, but there was no difference in ED50. The concentration-dependent increase in −d T/d t was unaffected. Gsα and Giα expression, cholera toxin- and pertussis toxin-induced ADP-ribosylation, and formation of the agonist-receptor-Gscomplex were unaffected by portal vein stenosis. Of the components of ECC examined, the caffeine-sensitive sarcoplasmic reticulum Ca2+pool was reduced 35%, although the Ca2+uptake and release processes were unchanged; the apparent density of L-type Ca2+channels decreased 60% with no change in affinity; the dihydropyridine Ca2+channel agonist BAY K 8644 produced relative changes in d T/d t that were similar in both groups, suggesting normal function in the remaining Ca2+channels; and Na+/Ca2+exchange was reduced 50% in the portal vein stenosis group. These data suggest that the effect of portal vein stenosis on the myocardium is the result of alterations to ECC.