To assess the role of verapamil (VER)-sensitive calcium (Ca2+) channels in the regional development and pathogenesis of isoproterenol (ISO)-induced cardiac hypertrophy, male Fischer rats (150-175 g, N = 51) were divided into control (C) and ISO-treated (I) and VER (V1, 100 mg/L drinking water; V2, 10 mg/kg ip twice daily) and no-VER subgroups. Rats began VER treatment 1 week before isoproterenol which was given subcutaneously by minipump (3 mg/kg/d) for 7 days. Mean total heart weight of all I rats was larger than C rats (p less than 0.05). Regionally, percent hypertrophy of the right ventricle (RV) was greater (p less than 0.05), while that of the atria tended to be greater (p = ns) than the left ventricle plus septum in ISO-treated rats (LVS: I, 20 +/- 5%; V1I, 19 +/- 3%; V2I, 22 +/- 6%; RV: I, 37 +/- 10%; V1I, 40 +/- 11%; V2I, 34 +/- 7%; atria: I, 64 +/- 21%; V1I, 54 +/- 56%; V2I, 51 +/- 28%). The total and regional hypertrophy of the heart produced by ISO was not affected by VER treatment. Isoproterenol produced diffuse and focal myocardial fibrosis in the subendomyocardium of the LVS with occasional foci of fibrosis in the RV and the subepimyocardium of the LVS. Quantitative analysis of picrosirius red-stained tissue sections demonstrated an increased volume percent of myocardial connective tissue limited to the subendomyocardium of the LVS in response to ISO (p less than 0.05). Verapamil partially reduced the ISO-induced fibrosis (p less than 0.05) (I, 7.04 +/- 1.01%; V1I, 4.06 +/- 0.28%; V2I, 3.87 +/- 0.27%).(ABSTRACT TRUNCATED AT 250 WORDS)