Minoxidil-induced cardiac hypertrophy in guinea pigs.
To investigate whether during cardiac hypertrophy changes occur in contractile protein composition and in mechanical and energetic properties of the myocardium, contractile protein composition, isometric force and adenosine triphosphate (ATP) consumption were studied in control and hypertrophied guinea-pig hearts. Cardiac hypertrophy was induced by adding minoxidil (120 or 200 mg/l) to the drinking water. Protein analysis was performed by one-dimensional gel electrophoresis. The myosin heavy-chain (MHC) composition was determined in an enzyme-linked immunosorbent assay (ELISA). ATP consumption and force development were simultaneously measured during isometric contraction in chemically skinned trabeculae. Histochemical analysis of cross-sectional area of cardiomyocytes and interstitial space was performed on the left ventricular tissue of 200 mg/l minoxidil-treated and control guinea pigs. Minoxidil treatment (120 and 200 mg/l) significantly increased left ventricular dry weight normalized for body weight by 19 +/- 4 and 24 +/- 4%, respectively. No significant differences were found in the cellular cross-sectional area, while interstitial space was slightly decreased in minoxidil-treated hearts. In left ventricular trabeculae of 200 mg/l minoxidil-treated guinea pigs, ATPase activity was slightly less than in those of control guinea pigs, whereas force did not differ significantly. Calcium sensitivity of force and ATPase activity were not affected by minoxidil treatment. Gel electrophoresis revealed no difference in contractile protein composition, but a tendency towards a lower amount of alpha-MHC in the minoxidil-treated hearts was found in ELISA.
van der Velden
J
J
Laboratory for Physiology, Free University, Amsterdam, The Netherlands. J.van_der_Velden.physiol@med.vu.nl
Borgdorff
P
P
Stienen
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D003285:Contractile Proteins / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006651:Histocytochemistry; D066298:In Vitro Techniques; D008914:Minoxidil / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D014665:Vasodilator Agents / Q000633:toxicity*
D003285:Contractile Proteins; D014665:Vasodilator Agents; D008914:Minoxidil; D000255:Adenosine Triphosphate; D018995:Myosin Heavy Chains; D002118:Calcium