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In this study we tested the hypothesis that vasostatins could actas myocardial modulators in the mammalian heart. Using the Langendorffperfusedrat heart, the cardiac effects of the two recombinant human CGAN-terminal fragments STA-CGA1-78 and STA-CGA1-115, containing thevasostatin-1 (CGA 1-76) and vasostatin-2 (CGA 1-113) sequences, respectively,were evaluated at concentrations of 11 165 nM. Cardiac performancewas evaluated by analyzing left ventricular pressure (LVP) and the rate pressureproduct (RPP: HR LVP), used as indexes of contractile activity andcardiac work, respectively. Under basal conditions, STA-CGA1-78 at all concentrationstested elicited a dose-dependent negative inotropism (LVP variationsranging from –9.6% ± 2 to –23% ± 2.9) without affecting coronarypressure (CP). In contrast, STA-CGA1-115 increased CP at 110 and 165 nMwithout affecting inotropism. Both STA-CGA1-78 and STA-CGA1-115 counteractedthe cardio-stimulatory effects of isoproterenol (ISO). The ISO-dependentpositive chronotropism was unaffected by STA-CGA1-78, while being reduced by STA-CGA1-115. Both peptides abolished the ISO-inducedpositive inotropism without modifying either the beta-adrenergic-dependentcoronary dilation or the ouabain-induced positive inotropism. The analysisof the percentage of variations of RPP in terms of EC50 values of ISO alone(–8.5 ± 0.3; r2 = 0.88) and in presence of STA-CGA1-78 (11, or 33, or 65 nM:–7.7 ± 0.15, r2 = 0.97; –7.7 ± 0.15, r2 = 0.97; –7.8 ± 0.78, r2 = 0.55, respectively)revealed a non-competitive type of antagonism of STA-CGA1-78. Takentogether, these

Recombinant N-terminal fragments of chromogranin-A modulate cardiac function of the Langendorff-perfused rat heart / Cerra, Maria Carmela; DE IURI, L; Angelone, Tommaso; Corti, A; Tota, B.. - In: BASIC RESEARCH IN CARDIOLOGY. - ISSN 0300-8428. - 101(1)(2006), pp. 43-52.

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