The cardiac pathophysiology role of the human recombinant Chromogranin A (CGA) N-terminal peptidic fragment vasostatin-1 (CGA 1–78; VS-1) was investigated on the Langendorff perfused rat heart. The name VS-1 reflects its ability to inhibit the vascular contraction evoked in several arterial and venous preparations by high potassium and by agonists such as noradrenaline and endothelin. Accordingly, VS-1 was proposed as a regulatory peptide protecting the cardiovascular system against stress responses, particularly under intense adrenergic stimulation (Helle, 2001). We found that on the unstimulated rat heart VS-1 elicited a dose-dependent negative inotropism and lusitropism without affecting coronary pressure. The negative inotropism was abolished by blocking β-adrenergic receptors, Gi/o proteins, and the Nitric Oxide (NO)-cGMP pathway. Under β-adrenergic stimulation (isoproterenol; ISO), VS-1 abolished the ISO-induced positive inotropism with a non-competitive type of antagonism. We also evaluated the possible role of VS-1 in limiting the extent of the necrosis induced by ischaemia and reperfusion (I/R). Evaluation of both infarct size with nitro-blue tetrazolium technique, and Lactic-dehydrogenase release measured in the effluent at regular intervals during reperfusion, show that VS-1 limits the damage caused by I/R. Inhibition of NO pathway indicates the protective activity being mediated by NO signalling. These data support our hypothesis that VS-1 acts as a novel cardioregulatory peptide in mammals. In fact it counteracts the β-adrenergic positive inotropic effect and shows cardioprotective effect.
Vasostatin-1: effect on myocardial contractility and cardioprotection
CAPPELLO, SANDRA;RASTALDO, Raffaella;PAGLIARO, Pasquale;
2007-01-01
Abstract
The cardiac pathophysiology role of the human recombinant Chromogranin A (CGA) N-terminal peptidic fragment vasostatin-1 (CGA 1–78; VS-1) was investigated on the Langendorff perfused rat heart. The name VS-1 reflects its ability to inhibit the vascular contraction evoked in several arterial and venous preparations by high potassium and by agonists such as noradrenaline and endothelin. Accordingly, VS-1 was proposed as a regulatory peptide protecting the cardiovascular system against stress responses, particularly under intense adrenergic stimulation (Helle, 2001). We found that on the unstimulated rat heart VS-1 elicited a dose-dependent negative inotropism and lusitropism without affecting coronary pressure. The negative inotropism was abolished by blocking β-adrenergic receptors, Gi/o proteins, and the Nitric Oxide (NO)-cGMP pathway. Under β-adrenergic stimulation (isoproterenol; ISO), VS-1 abolished the ISO-induced positive inotropism with a non-competitive type of antagonism. We also evaluated the possible role of VS-1 in limiting the extent of the necrosis induced by ischaemia and reperfusion (I/R). Evaluation of both infarct size with nitro-blue tetrazolium technique, and Lactic-dehydrogenase release measured in the effluent at regular intervals during reperfusion, show that VS-1 limits the damage caused by I/R. Inhibition of NO pathway indicates the protective activity being mediated by NO signalling. These data support our hypothesis that VS-1 acts as a novel cardioregulatory peptide in mammals. In fact it counteracts the β-adrenergic positive inotropic effect and shows cardioprotective effect.
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