Insulin and insulin-like growth factor-I cause vasorelaxation in human vessels in vitro

• Published in: Coronary artery disease Vol. 11; no. 1; pp. 69 - 76
• Main Authors: Izhar, Uzi, Hasdai, David, Richardson, Darcy M, Cohen, Pinchas, Lerman, Amir
• Format: Journal Article
• Language: English
• Published: England Lippincott Williams & Wilkins, Inc 01-02-2000
• Subjects: Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Humans; In Vitro Techniques; Insulin - physiology; Insulin-Like Growth Factor I - physiology; Mammary Arteries - physiology; Nitric Oxide - metabolism; Saphenous Vein - physiology; Vasodilation - physiology
• ISSN: 0954-6928; 1473-5830
• DOI: 10.1097/00019501-200002000-00012

BACKGROUNDInsulin and insulin-like growth factor-I (IGF-I) are endogenous peptides with vasoactive activities.
OBJECTIVETo evaluate the vasodilatory effects of insulin and IGF-I on human vessels taken from patients with and without noninsulin-dependent diabetes mellitus (NIDDM) and to elucidate their mechanisms of action.
METHODSVascular rings of human internal mammary artery (IMA) and saphenous vein harvested from 54 patients with and without NIDDM undergoing coronary bypass surgery were studied in vitro.
RESULTSFor samples from patients without NIDDM both insulin and IGF-I (10 –10 mol/l) evoked greater relaxation in IMA rings (30±4 and 29±6%, maximal relaxation±SEM, respectively) than they did in saphenous-vein rings (43±4 and 42±5%, respectively, P <0.05 both for insulin and for IGF-I). Similar results were obtained with vessels from patients with NIDDM. Relaxation was not affected by the removal of the endothelium and by inhibition of the production of nitric oxide. However, the vascular relaxation caused by insulin and IGF-I was completely abolished by KCl, and was attenuated by the nonspecific potassium-channel blocker tetraethylammonium (for IMA rings, to 77±8 and 66±4% with insulin and IGF-I, respectively; for saphenous vein rings, 73±2 and 77±1% for insulin and IGF-I, respectively, P <0.001).
CONCLUSIONSBoth insulin and IGF-I induced endothelial-independent, nitric oxide-independent vasorelaxation of rings from human IMA and saphenous veins, through a mechanism involving activation of potassium channels. This response remained intact in vessels from patients with NIDDM. This result supports the hypothesis that insulin and IGF-I play roles in the regulation of vascular tone in human vessels.