title: Effects of zofenopril on cardiac sarcoplasmic reticulum calcium handling.
abstract: Isolated rat hearts were perfused for 120 minutes in the presence or in the absence of 10 microM zofenoprilat, the active metabolite of zofenopril. At the end of perfusion, cardiac tissue was used to assay sarcoplasmic reticulum (SR) (45)Ca uptake and SR calcium release, which was determined by automatized quick filtration technique after SR vesicle loading with (45)Ca. The expression of genes involved in the control of calcium homeostasis was evaluated by polymerase chain reaction after reverse transcription. In chronic experiments, SR (45)Ca uptake and gene expression were measured in hearts derived from rats treated with 15 mg*kg(-1)*day(-1) zofenopril for 15 days. Acute or chronic zofenopril administration did not produce any change in contractile performance. In acute experiments, SR (45)Ca uptake was significantly increased after exposure to zofenoprilat. The rate constant of calcium-induced calcium release was slightly although not significantly higher, and the calcium leak measured under conditions promoting SR channel closure was significantly increased. In the chronic model, significant increase in the rate of SR (45)Ca uptake was confirmed. Gene expression was not modified, except for decreased phospholamban expression, which is observed in the acute but not in the chronic model. In conclusion, zofenopril increases SR calcium cycling and stimulates active calcium uptake into the SR.
authors.affiliation: Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Frascarelli
authors.forename: Vittoria
authors.initials: V
authors.lastname: Carnicelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Ghelardoni
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.forename: Francesca
authors.initials: F
authors.lastname: Ronca
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C044958:zofenopril; D002216:Captopril; D002118:Calcium