Modulation of cardiac contractility through endothelin-1 release and myocardial mast cell degranulation.

The aim of this study was to outline the consequences of a hypertonic saline-dextran-40 (HSD) infusion-induced peripheral flow stimulus on the ventricular function in closed-chest, pentobarbital-anesthetized dogs. We hypothesized that HSD-induced elevation in endothelin-1 (ET-1) and nitric oxide (NO) release can have a role in myocardial contractile responses; and that cardiac mast cells (MC) degranulation may be involved in this process. The consequences of disodium cromoglycate (a MC stabilizer) or ETR-p1/fl peptide (an endothelin-A receptor antagonist) treatment were evaluated. A 4 ml/kg iv HSD40 infusion significantly increased cardiac index and myocardial contractility, and resulted in a decreased peripheral resistance. The postinfusion period was characterized by significant plasma NO and ET-1 elevations, these hemodynamic and biochemical changes being accompanied by a decreased myocardial ET-1 content, NO synthase activity and enhanced myocardial MC degranulation. Disodium cromoglycate treatment inhibited the HSD40-induced elevations in myocardial contractility and MC degranulation, and similar hemodynamic changes were noted after treatment with ETR-p1/fl peptide, together with a normalized myocardial myocardial ET-1 content, NO synthesis and a significant reduction in MC degranulation. These results indicate that peripheral NO and ET-1 release modulates the cardiac contractility through myocardial ET-A receptor activation and MC degranulation.