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.
Eszlári
E
E
Institute of Surgical Research, University of Szeged, Szeged, Hungary.
Czóbel
M
M
Molnár
G
G
Bogáts
G
G
Kaszaki
J
J
Nagy
S
S
Boros
M
M
D000818:Animals; D001810:Blood Volume / Q000502:physiology; D015550:Cell Degranulation / Q000502:physiology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D004285:Dogs; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood; D010455:Peptides / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000494:pharmacology
D003911:Dextrans; C109027:ETR-p1-f1 antisense peptide; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D044022:Receptor, Endothelin A; D012462:Saline Solution, Hypertonic; D009569:Nitric Oxide; D004205:Cromolyn Sodium