Normal responsiveness to external Ca and to Ca-channel modifying agents in hypertrophied rat heart.
In rat heart, the maximum velocity of shortening is decreased in response to chronic pressure overload. This is in part explained by an isomyosin shift, but several arguments suggest changes in membrane proteins. Inotropic response to calcium channel modifiers and to external calcium were simultaneously determined to explore this possibility. Left ventricular hypertrophy was induced by abdominal aortic stenosis and after 4-5 wk the left ventricular-to-body weight ratio increased by 61%. The effects of BAY K 8644 (10(-9) to 10(-6) M), a calcium channel activator, nifedipine (10(-9) to 10(-7) M), and external calcium (0.25-2.50 mM) were studied on isolated hearts at a coronary flow of 20 ml.min-1.g of left ventricle-1. The inotropic response (in percent changes in developed pressure and in dP/dtmax) was unmodified in the hypertrophied hearts. This work is in agreement with previous findings that both the total number of dihydropyridine binding sites and the peak magnitude of calcium current increase in proportion to the degree of hypertrophy. It suggests that the slowing of velocity could not be explained by a decreased number of Ca2+ channels but may more likely reflect modifications of the sarcomeres or sarcoplasmic reticulum.
Institut National de la Santé et de Recherche Médicale (INSERM) U127, Hôpital, Paris, France.
F
F
Callens-el Amrani
E
E
Mayoux
C
C
Mouas
R
R
Clapier-Ventura
D
D
Henzel
D
D
Charlemagne
B
B
Swynghedauw
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006332:Cardiomegaly / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002121:Calcium Channel Blockers; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium