title: The NO stimulator, Catestatin, improves the Frank-Starling response in normotensive and hypertensive rat hearts.
abstract: The myocardial response to mechanical stretch (Frank-Starling law) is an important physiological cardiac determinant. Modulated by many endogenous substances, it is impaired in the presence of cardiovascular pathologies and during senescence. Catestatin (CST:hCgA352-372), a 21-amino-acid derivate of Chromogranin A (CgA), displays hypotensive/vasodilatory properties and counteracts excessive systemic and/or intra-cardiac excitatory stimuli (e.g., catecholamines and endothelin-1). CST, produced also by the myocardium, affects the heart by modulating inotropy, lusitropy and the coronary tone through a Nitric Oxide (NO)-dependent mechanism. This study evaluated the putative influence elicited by CST on the Frank-Starling response of normotensive Wistar-Kyoto (WKY) and hypertensive (SHR) hearts by using isolated and Langendorff perfused cardiac preparations. Functional changes were evaluated on aged (18-month-old) WKY rats and SHR which mimic human chronic heart failure (HF). Comparison to WKY rats, SHR showed a reduced Frank-Starling response. In both rat strains, CST administration improved myocardial mechanical response to increased end-diastolic pressures. This effect was mediated by EE/IP3K/NOS/NO/cGMP/PKG, as revealed by specific inhibitors. CST-dependent positive Frank-Starling response is paralleled by an increment in protein S-Nitrosylation. Our data suggested CST as a NO-dependent physiological modulator of the stretch-induced intrinsic regulation of the heart. This may be of particular importance in the aged hypertrophic heart, whose function is impaired because of a reduced systolic performance accompanied by delayed relaxation and increased diastolic stiffness.
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy; National Institute of Cardiovascular Research, Bologna, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Angelone
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Quintieri
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Pasqua
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Filice
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cantafio
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Scavello
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rocca
authors.affiliation: Department of Medicine, University of California & VA San Diego Healthcare System, San Diego, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Mahata
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy. Electronic address: alfonsina.gattuso@unical.it.
authors.forename: A
authors.initials: A
authors.lastname: Gattuso
authors.affiliation: Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy; National Institute of Cardiovascular Research, Bologna, Italy. Electronic address: maria_carmela.cerra@unical.it.
authors.forename: M C
authors.initials: MC
authors.lastname: Cerra
keywords: Catestatin; Chromogranins; Heart; Intracellular signaling; Nitric oxide