title: Cardiac excitation-contraction coupling in the portal hypertensive rat.
abstract: Basal contractility and responses to beta-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, beta-adrenoceptor-G protein coupling, and excitation-contraction coupling (ECC). Contractility (dT/dt) was reduced 30-50% in right and left ventricles, but the rate of relaxation (-dT/dt) was unaffected. Isoproterenol-induced positive inotropism was diminished, but there was no difference in ED(50). The concentration-dependent increase in -dT/dt was unaffected. G(s)alpha and G(i)alpha expression, cholera toxin- and pertussis toxin-induced ADP-ribosylation, and formation of the agonist-receptor-G(s) complex were unaffected by portal vein stenosis. Of the components of ECC examined, the caffeine-sensitive sarcoplasmic reticulum Ca(2+) pool was reduced 35%, although the Ca(2+) uptake and release processes were unchanged; the apparent density of L-type Ca(2+) channels decreased 60% with no change in affinity; the dihydropyridine Ca(2+) channel agonist BAY K 8644 produced relative changes in dT/dt that were similar in both groups, suggesting normal function in the remaining Ca(2+) channels; and Na(+)/Ca(2+) 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.
authors.affiliation: Department of Pharmacology, Louisiana State University Health Sciences Center, Shreveport 71130, USA. jzavec@lsumc.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Zavecz
authors.forename: O
authors.initials: O
authors.lastname: Bueno
authors.forename: R E
authors.initials: RE
authors.lastname: Maloney
authors.forename: J M
authors.initials: JM
authors.lastname: O'Donnell
authors.forename: S C
authors.initials: SC
authors.lastname: Roerig
authors.forename: H D
authors.initials: HD
authors.lastname: Battarbee
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D006975:Hypertension, Portal / Q000188:drug therapy / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D017275:Isradipine / Q000378:metabolism / Q000494:pharmacology; D008026:Ligation; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009210:Myofibrils / Q000378:metabolism; D010210:Papillary Muscles / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D037342:Pertussis Toxin; D011169:Portal Vein; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014316:Tritium; D016276:Ventricular Function; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D014316:Tritium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002772:Cholera Toxin; D012964:Sodium; D037342:Pertussis Toxin; D019205:GTP-Binding Protein alpha Subunits, Gs; D007545:Isoproterenol; D002118:Calcium; D017275:Isradipine