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Recent evidence from both mammalian and non-mammalian vertebrates supports a role for paracrine modulation of myocardial function by the endocardial endothelium (EE) cells. Like the secretory function of the vascular endothelium, this role involves the release of cardioactive factors such as nitric...
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| Language: | English |
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| Online Access: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.619.3869 http://www-heb.pac.dfo-mpo.gc.ca/congress/2002/Randall/tota.pdf |
| Summary: | Recent evidence from both mammalian and non-mammalian vertebrates supports a role for paracrine modulation of myocardial function by the endocardial endothelium (EE) cells. Like the secretory function of the vascular endothelium, this role involves the release of cardioactive factors such as nitric oxide (NO), endothelin-1, atrial natriuretic peptides, prostanoids and a number of other substances that have been well characterised in bioassay studies. Endothelial cells also possess enzymatic activities, in particular ACE/kininase activity, which can alter local levels of angiotensin II and bradykinin. Using isolated working heart preparations of teleosts (Imbrogno et al., 2001; Gattuso et al., 2002) and amphibians (Sys et al., 1997) previously set up in our lab, we have explored the role of the EE as a source of cardioactive substances and as a sensor of luminal blood flow-related mechanical and chemical stimuli. To analyse the specific autocrine role of the EE without the confounding effects of the vascular endothelium, we used as a natural model juvenile eel (fresh water Anguilla anguilla) hearts in which the compact ventricular layer and the coronary circulation are poorly developed. We found that under basal conditions the EE produces NO in amounts sufficient to exert a negative inotropism on the myocardium via a cGMP-dependent mechanism. The NO signal is abrogated by the functional damage of the EE, indicating that EE transduces mechanical stimulation into NO release. The EE mediates via a NO-cGMP pathway the positive inotropism elicited by luminal 25 26 cholinergic stimuli, hence partecipating in the ventricular fine-tuning of the molecular signalling cascade downstream from the stimulation of the cardiac muscarinic receptors (Imbrogno et al., 2001). Moreover, the functional integrity of the EE is a prerequisite for mediating intracavitary Angiotensin II-mediated inotropic signals, since these are abolished by functional damage of the EE by |
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