Vasorelaxant effect of glucagon-like peptide-(7-36)amide and amylin on the pulmonary circulation of the rat.
The gastrointestinal peptides glucagon-like peptide-1(7-36)amide (GLP-1) and amylin are currently being tested in clinical trials for the treatment of diabetes mellitus due to their effects in lowering blood glucose. Receptors for these polypeptides also exist in the lung and since polypeptides are known to modulate airway and pulmonary vascular tone, we investigated whether GLP-1 and amylin act similarly in the lung. We compared their effects with the well-known actions of calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP). Both GLP-1 and amylin induced a dose-dependent and time-reversible endothelial-dependent relaxation of preconstricted pulmonary artery rings. Amylin was approximately as strong as VIP and CGRP, GLP-1 however, was 2.3-fold less potent. GLP-1 as well as amylin also reduced the vascular tone in the isolated, perfused and ventilated rat lung. In contrast to their action on the pulmonary vasculature, neither GLP-1 nor amylin showed any effect on the tone of isolated preconstricted trachea rings. In conclusion, GLP-1 and amylin represent two additional peptides which may modulate pulmonary vascular tone.
Golpon
H A
HA
Department of Internal Medicine, Philipps University of Marburg, Baldinger Strasse, 35033, Marburg, Germany.
Puechner
A
A
Welte
T
T
Wichert
P V
PV
Feddersen
C O
CO
D000109:Acetylcholine / Q000494:pharmacology; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D012123:Pulmonary Ventilation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000682:Amyloid; D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D005768:Gastrointestinal Hormones; D058228:Islet Amyloid Polypeptide; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C055453:glucagon-like peptide 1 (7-36)amide; D014660:Vasoactive Intestinal Peptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine