Pulmonary vasodilation in the rat by insulin in vitro could indicate potential hazard for inhaled insulin

• Published in: Diabetologia 2003-09, Vol.46 (9), p.1199-1202
• Main Authors: AYE, M, SHEEDY, W, HARRISON, R, THOMPSON, J. S, MORICE, A. H, MASSON, E. A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Diabetes; Diabetes. Impaired glucose tolerance; Dinoprost - pharmacology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Human papillomavirus; Hypoxia; Insulin; Insulin - pharmacology; Laboratory animals; Lung diseases; Male; Medical sciences; Muscle Contraction - drug effects; Nitric oxide; Pulmonary arteries; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Rats; Rats, Wistar; Vasodilation - drug effects; Veins & arteries
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-003-1172-y

Hypoxic pulmonary vasoconstriction is an essential mechanism to prevent hypoxaemia in lung diseases. Insulin is known to be a systemic vasodilator but its effect on the pulmonary circulation is not known. Inhaled particulate insulin can generate locally high concentrations in the lung which could be physiologically important. We therefore studied the effects of insulin in vitro on isolated rat pulmonary artery in a small vessel myograph. We have shown that pulmonary artery vasodilatation with insulin occurs in a dose-dependent manner. Pre-constriction with PGF2alpha can be abolished (105.7+/-2.9%, mean+/-SEM) and pre-constriction with hypoxia reduced (68.9+/-6.5%) by pharmacologically relevant concentrations of insulin. The characteristic phasic vasoconstriction by pulmonary vessel to hypoxia is substantially modified, resulting in sustained vasodilatation. These effects could be clinically important for patients using inhaled insulins who have acute or occult chronic lung disease.