title: Cardiac heterometric response: the interplay between Catestatin and nitric oxide deciphered by the frog heart.
abstract: The length-active tension relation or heterometric regulation (Frank-Starling mechanism) is modulated by nitric oxide (NO) which, released in pulsatile fashion from the beating heart, improves myocardial relaxation and diastolic distensibility. The NO signaling is also implicated in the homeometric regulation exerted by extrinsic factors such as autonomic nervous system, endocrine and humoral agents. In the in vitro working frog heart, the Chromogranin A (CGA)-derived peptide, Catestatin (CTS; bovine CGA344-364), exerts a direct cardio-suppressive action through a NOS-NO-cGMP-mediated mechanism which requires the functional integrity of the endocardial endothelium (EE) and its endothelin-1 B type (ETB) receptor. However, functional interplay between NO and CTS and their role in the Frank-Starling response of the frog heart are lacking. Here we show that CTS improves the sensitivity to preload increases similar to that exerted by NO. This effect is abolished by inhibition of NO synthase (L-NAME), guanylate cyclase (ODQ), protein kinase G (KT5823), PI3K (Wortmannin), as well as by the functional damage of EE (Triton X-100) suggesting that CTS operates through an EE-dependent NO release. On the whole, the use of the avascular frog heart revealed the EE as major sensor-transducer interface between the physical (volume load) and chemical (CTS) stimuli, NO functioning as a connector between heterometric and homeometric regulation.
authors.affiliation: Department of Cell Biology, University of Calabria, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Mazza
authors.forename: Teresa
authors.initials: T
authors.lastname: Pasqua
authors.forename: Alfonsina
authors.initials: A
authors.lastname: Gattuso
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053379:Chromogranin A / Q000378:metabolism*; D004699:Endocardium / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011898:Ranidae; D013318:Stroke Volume / Q000187:drug effects*
chemical_list: D053379:Chromogranin A; D020030:Nitric Oxide Donors; D010446:Peptide Fragments; C109084:chromogranin A (344-364); D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium