Occurrence and effects of endothelin in guinea-pig cardiopulmonary tissue.
Endothelin-like immunoreactivity (-LI) was present in the guinea-pig cardiopulmonary tissues with the associated autonomic neural supply. The highest levels were found in the stellate ganglion (15 pmol g-1) followed by the vagus nerve, pulmonary artery, lung and right atrium of the guinea-pig. Endothelin I, but not endothelin III, induced an increase in contractile force and frequency followed by an atropine-resistant inhibition of right atrial contractility at higher concentrations. Exposure to endothelin I caused a pronounced, long-lasting coronary vasoconstriction as revealed by a decrease in perfusate outflow. In addition, both heart and contractile force were attenuated. Guinea-pig bronchi in vitro contracted upon exposure to endothelin I and III, but only endothelin I caused contraction of pulmonary arteries. The C-terminal hexapeptide of endothelin I did not influence right atrial, bronchial or pulmonary artery contractility. Endothelin I increased the mean arterial pressure and insufflation pressure and decreased the heart rate in the guinea-pig in vivo. In conclusion, endothelin-LI is present in the cardiovascular, respiratory and nervous tissues of the guinea-pig and endothelin induces strong coronary and pulmonary vasoconstrictor effects. The effects on atrial contractile force and frequency are concentration-dependent with stimulation at lower and inhibition at higher concentrations. Based on the diversity in response to endothelin III in the bronchi compared to atrium and pulmonary artery, it may be suggested that different receptor populations exist in bronchial and cardiovascular muscle, although the cellular localization and forms of endothelin present in guinea-pig cardiopulmonary tissue remain to be established.
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
A
A
Franco-Cereceda
R
R
Matran
Y P
YP
Lou
J M
JM
Lundberg
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016232:Endothelins; D005724:Ganglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011863:Radioimmunoassay; D014630:Vagus Nerve / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016232:Endothelins; D010455:Peptides