Effect of endothelin-1 on pulmonary resistance in rats.
We examined the effect of endothelin-1 (ET-1), a novel 21-residue vasoconstrictor peptide, on pulmonary resistance (RL) in Wistar rats. The lung volume, tracheal flow, and transpulmonary pressure of tracheotomized and paralyzed rats were measured with a fluid-filled esophageal catheter and a pressure-sensitive body plethysmograph. RL was calculated by the method of von Neergaard. The femoral artery was cannulated to measure the mean arterial blood pressure. Intravenous bolus administration of synthetic ET-1 provoked a dose-dependent increase in RL in rats. The bronchoconstricting effect reached maximum at 500 pmol/kg. This bronchoconstriction was observed in less than 5 min, increased up to 15 min, and was sustained for 60 min. ET-1 increased the mean arterial blood pressure in a dose-dependent manner. We conclude that ET-1 is a hitherto unknown potent bronchoconstrictor that has a sustained effect in vivo. The potential physiological and pathophysiological role of this new peptide in the development of respiratory disease warrants further investigation.
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
T
T
Matsuse
Y
Y
Fukuchi
T
T
Suruda
T
T
Nagase
Y
Y
Ouchi
H
H
Orimo
D000403:Airway Resistance / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents