Basic Research in Cardiology

, Volume 101, Issue 1, pp 43–52

Recombinant N–terminal fragments of chromogranin–A modulate cardiac function of the Langendorff–perfused rat heart

  • M. C. Cerra
  • L. De Iuri
  • T. Angelone
  • A. Corti
  • B. Tota
ORIGINAL CONTRIBUTION

DOI: 10.1007/s00395-005-0547-2

Cite this article as:
Cerra, M.C., De Iuri, L., Angelone, T. et al. Basic Res Cardiol (2006) 101: 43. doi:10.1007/s00395-005-0547-2

Abstract

In this study we tested the hypothesis that vasostatins could act as myocardial modulators in the mammalian heart. Using the Langendorff–perfused rat heart, the cardiac effects of the two recombinant human CGA N–terminal fragments STA–CGA1–78 and STA–CGA1–115, containing the vasostatin–1 (CGA 1–76) and vasostatin–2 (CGA 1–113) sequences, respectively, were evaluated at concentrations of 11 ÷ 165 nM. Cardiac performance was evaluated by analyzing left ventricular pressure (LVP) and the rate pressure product (RPP: HR × LVP), used as indexes of contractile activity and cardiac work, respectively. Under basal conditions, STA–CGA1–78 at all concentrations tested elicited a dose–dependent negative inotropism (LVP variations ranging from –9.6% ± 2 to –23% ± 2.9) without affecting coronary pressure (CP). In contrast, STA–CGA1–115 increased CP at 110 and 165 nM without affecting inotropism. Both STA–CGA1–78 and STA–CGA1–115 counteracted the cardio–stimulatory effects of isoproterenol (ISO). The ISO–dependent positive chronotropism was unaffected by STA–CGA1–78, while being reduced by STA–CGA1–115. Both peptides abolished the ISO–induced positive inotropism without modifying either the β–adrenergic–dependent coronary dilation or the ouabain–induced positive inotropism. The analysis of 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. Taken together, these data suggest vasostatins as novel cardioregulatory peptides in mammals.

Key words

vasostatins chromogranin A cardiac performance myocardial contractility adrenergic modulation 

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • M. C. Cerra
    • 1
    • 2
  • L. De Iuri
    • 1
  • T. Angelone
    • 1
    • 2
  • A. Corti
    • 3
  • B. Tota
    • 2
  1. 1.Department of Pharmaco-BiologyUniversity of CalabriaArcavacata di Rende (CS)Italy
  2. 2.Department of Cell BiologyUniversity of CalabriaArcavacata di Rende (CS)Italy
  3. 3.DIBIT-San Raffaele HScientific InstituteMilanItaly

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