Fivefold administration of L-type Ca 2+ channel blocker verapamil in a dose of 1.5 mg/kg to newborn rats increased the parameters of DNA-synthetic activity in the myocardium: labeling index and intensity increased 1.24-fold on average. Body weight decreased with simultaneous increase in the absolute and relative heart weight. Morphometric parameters of the nucleus and nucleoli were practically unaffected. Our findings suggest that the Ca 2+ channel blocker verapamil administered at the early postnatal stages can modulate morphogenesis of the heart. Key Words: Ca 2+ channels; DNA synthesis; myocardium; nucleolar organizer; ontogeny Influences on the heart in the early postnatal ontogeny considerably modulate its sensitivity to damaging factors in adults [3]. L-type voltage-dependent Ca 2 § channels appear in the early postnatal period, which allows to use verapamil in pediatrics [10,11]. Ca > channel blockers improve heart recovery after myocardial infarction and stimulate fibroblast proliferation in cell culture [7,12]. At the same time verapamil inhibits proliferation of smooth muscle cells in the intima of blood vessels during atherosclerosis development [4] and proliferation of B cells in mice in response to Tdependent antigen [9]. In light of this, of particular interest is to study the effect of verapamil on DNA synthesis in the myocardium of newborn rats.
MATERIALS AND METHODSExperiments were carried out on 43 rat pups. Veraparail (in 2-ml ampoules, 50 mg per ampoule, Knoll) was administered intraperitoneally in a dose of 1.5 mg/kg on days 2 through 6 between 11.0 and 13.00. Control animals received equivalent volume of isotonic NaC1. The animals were decapitated one day after the last inCentral Research Laboratory, Far-East State Medical University, Khabarovsk jection. 3H-thymidine (specific activity 1530 TBq/mol) was injected intraperitoneally in a dose of 1 gCi/g body weight 1 h before sacrifice.Parameters of DNA synthesis: labeling index (LI, %) and label intensity (mean number of silver grains over nucleus) were assessed on histotopographic sections in 10 myocardial areas: subendocardial, intramural, and subepicardial layers of the left and right ventricles, subendocardial and intramural layers of the interventricular septum, and in the left and right atria. The dynamics of the body weight and the absolute and relative weight of the heart (heart weight/body weight ratio at sacrifice) were evaluated.The data were processed statistically using the Student t test.