The Frank -Starling mechanism is a fundamental property of the vertebrate heart, which allows the myocardium to respond to increased filling pressure with a more vigorous contraction of its lengthened fibres. In mammals, myocardial stretch increases cardiac nitric oxide (NO) release from both vascular endothelium and cardiomyocytes. This facilitates myocardial relaxation and ventricular diastolic distensibility, thus influencing the Frank -Starling mechanism.In the in vitro working heart of the eel Anguilla anguilla, we previously showed that an endogenous NO release affects the Frank -Starling response making the heart more sensitive to preload. Using the same bioassay, we now demonstrate that this effect is confirmed in the presence of the exogenous NO donor S-nitroso-N-acetyl penicillamine, is independent from endocardial endothelium and guanylate cyclase/ cGMP/protein kinase G and cAMP/protein kinase A pathways, involves a PI(3)kinase-mediated activation of endothelial NO synthase and a modulation of the SR-CA 2þ ATPase (SERCA2a) pumps. Furthermore, we show that NO influences cardiac response to preload through S-nitrosylation of phospholamban and consequent activation of SERCA2a. This suggests that in the fish heart NO modulates the Frank -Starling response through a beat-to-beat regulation of calcium reuptake and thus of myocardial relaxation.We propose that this mechanism represents an important evolutionary step for the stretch-induced intrinsic regulation of the vertebrate heart, providing, at the same time, a stimulus for mammalian-oriented studies.
The conus (bulbo-ventricular) valves of teleosts perform a key function in the control of blood backflow during ventricular diastole. However, the structural characteristics of these valves are almost unknown. This paper presents a systematic anatomical, histological and structural study of the conus valves of the adult gilthead seabream (Sparus auratus). S. auratus shows two major left and right valves consisting of the leaflet and the supporting sinus. Each valvar leaflet can be divided into a stout proximal body and a flap-like distal region. The proximal body is structured into three layers: a luminal fibrosa, a dense cellular core and a parietal fibrosa. The luminal fibrosa is a collagenous structure extending the entire length of the leaflet, while the parietal fibrosa is restricted to the most proximal area. The dense cellular core consists of fibroblastic cells and a matrix rich in glycoconjugates, collagen and elastin.The histochemical and structural data suggest that the luminal fibrosa bears most of the force associated with valvar closure, while the cellular core acts as a cushion dampening vibrations and absorbing the elastic recoil. The sinus wall is a fibrous layer which shows proximal-distal differences in thickness. It also shows compositional differences that can be related to mechanical function. We describe the presence of a fibrous cylinder formed by the sinus wall, the fibrous interleaflet triangles and the fibrous layer that covers the inner surface of the conus myocardium. This fibrous cylinder constitutes the structural nexus between the ventricle, the conus and the bulbus arteriosus, provides support for the conus valves and separates the valvar complex from the surrounding tissues. The structure of the conus valves in S. auratus is different from that found in other vertebrates. Anatomical similarities between the conus valves and the mammalian arterial valves are emphasized. Each phyletic group appears to have developed specific structures in order to perform similar functions.
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