Mechanism of coronary vasodilation to insulin and insulin-like growth factor I is dependent on vessel size

Abstract

Insulin and insulin-like growth factor I (IGF-I) influence numerous metabolic and mitogenic processes; these hormones also have vasoactive properties. This study examined mechanisms involved in insulin- and IGF-I-induced dilation in canine conduit and microvascular coronary segments. Tension of coronary artery segments was measured after constriction with PGF(2alpha). Internal diameter of coronary microvessels (resting diameter = 112.6+/-10.1 microm) was measured after endothelin constriction. Vessels were incubated in control (Krebs) solution and were treated with N(omega)-nitro-L-arginine (L-NA), indomethacin, or K(+) channel inhibitors. After constriction, cumulative doses of insulin or IGF-I (0.1-100 ng/ml) were administered. In conduit arteries, insulin produced modest maximal relaxation (32 +/- 5%) compared with IGF-I (66+/-12%). Vasodilation was attenuated by nitric oxide synthase (NOS) and cyclooxygenase inhibition and was blocked with KCl constriction. Coronary microvascular relaxation to insulin and IGF-I was not altered by L-NA, indomethacin, tetraethylammonium chloride, glibenclamide, charybdotoxin, and apamin; however, tetrabutylammonium chloride attenuated the response. In conclusion, insulin and IGF-I cause vasodilation in canine coronary conduit arteries and microvessels. In conduit vessels, NOS/cyclooxygenase pathways are involved in the vasodilation. In microvessels, relaxation to insulin and IGF-I is not mediated by NOS/cyclooxygenase pathways but rather through K(+)-dependent mechanisms.

Impaired Insulin-Like Growth Factor I Vasorelaxant Effects in Hypertension

“…Our receptor analysis, however, cannot exclude a difference in IGF-I receptor binding or affinity between the 2 rat strains. Because several studies have demonstrated that both endothelial NO 12,13,23 and potassium channels mediate IGF-I vascular action, 14,15,24 we extended our observations to characterize the role of these components in the abnormal vascular response to IGF-I in hypertensive rats. In regard to this issue, it is important to emphasize that vasorelaxation evoked by NO is also realized by smooth muscle potassium channels.…”

“…Our findings are supported by a recent observation that IGF-I vasodilation in conduit vessels is attenuated by L-NAME and completely blocked by KCl. 24 During the removal of endothelium or the inhibition of …”

Insulin-Induced Generation of Reactive Oxygen Species and Uncoupling of Nitric Oxide Synthase Underlie the Cerebrovascular Insulin Resistance in Obese Rats

“…Insulin, a metabolic hormone, has been known to exert vasodilator (Chen and Messina, 1996;Katakam et al, 2005;Oltman et al, 2000Oltman et al, , 2006 as well as vasoconstrictor (Eringa et al, 2002;Katakam et al, 2009a;Miller et al, 2002;van Veen and Chang, 1998) effects on several diverse vascular beds. Recently, we identified insulin receptors in rat cerebral arteries and have reported the cerebrovascular actions of insulin (Katakam et al, 2009b).…”

Insulin-like growth factor-I inhibits rat arterial KATP channels through pI 3-kinase

“…Cultured human intestinal smooth muscle cells release IGF-I, which stimulates their growth by activation of both mitogen-activated protein kinase (MAP kinase) and phosphoinositide 3-kinase (PI 3-kinase) signalling cascades [3]. In addition to its metabolic and growth-promoting properties, IGF-I has rapid vasoactive effects which range from vasoconstriction to vasodilation depending on the vascular bed, vessel size and species [4][5][6][7]. In rat mesenteric arteries, IGF-I potentiates the vasoconstriction induced by arginine vasopressin [8], and in primary cultures of smooth muscle cells from these arteries IGF-I increases intracellular Ca 2+ concentration [6].…”

“…In rat mesenteric arteries, IGF-I potentiates the vasoconstriction induced by arginine vasopressin [8], and in primary cultures of smooth muscle cells from these arteries IGF-I increases intracellular Ca 2+ concentration [6]. Some of the rapid effects of IGF-I may occur through actions on ion channels and it has been suggested that modulation of K + channel activity may underlie some of these vasoactive effects [5]. Further, insulin or IGF-I can prevent leptininduced activation of ATP-sensitive K + (K ATP ) channels in rat CRI-G1 insulin-secreting cells [9].…”