Glucose-induced alterations of cytosolic free calcium in cultured rat tail artery vascular smooth muscle cells.

Abstract

We have previously suggested that hyperglycemia per se may contribute to diabetic hypertensive and vascular disease by altering cellular ion content. To more directly investigate the potential role of glucose in this process, we measured cytosolic free calcium in primary cultures of vascular smooth muscle cells isolated from Sprague-Dawley rat tail artery before and after incubation with 5 (basal), 10, 15, and 20 mM glucose. Glucose significantly elevated cytosolic free calcium in a dose-and time-dependent manner, from 110.0±5.4 to 124.5±9.0, 192.7±20.4, and 228.4+21.9 nM at 5, 10, 15, and 20 mM glucose concentrations, respectively. This glucose-induced cytosolic free calcium elevation was also specific, no change being observed after incubation with equivalent concentrations of L-glucose or mannitol. This glucose effect was also dependent on extracellular calcium and pH, since these calcium changes were inhibited in an acidotic or a calcium-free medium, or by the competitive calcium antagonist lanthanum.We conclude that ambient glucose concentrations within clinically observed limits may alter cellular calcium ion homeostasis in vascular smooth muscle cells. We suggest that these cellular ionic effects of hyperglycemia may underlie the predisposition to hypertension and vascular diseases among diabetic subjects and/or those with impaired glucose tolerance. (J. Clin. Invest. 1995. 95:763-767.)

Vascular targets of redox signalling in diabetes mellitus

“…3). This study is in line with findings in the rat tail artery, where hyperglycaemia was found to initiate alterations of cytosolic Ca 2+ signalling [175]. This was accompanied by ROS-triggered restructuring of the cytoskeleton and the endoplasmic reticulum.…”

Effects of age, gender and metabolic factors on endothelium‐dependent vasodilation: a population‐based study

“…Elevated glucose levels could impair EDV by several mechanisms, such as an activation of the polyol pathway resulting in a decline in the NO synthesis cofactor NADPH and a decline in the activity of the Na,KATPase, oxygen free radical formation and activa-tion of protein kinase C [36±39]. On the other hand, both formation of advanced glycosylation endproducts (AGEs) and an increase in intracellular calcium in vascular smooth muscle cells induced by elevated glucose levels could attenuate both EDV and EIDV [40,41]. It should, however, be emphasized that whatever mechanisms are involved, they act also in the normoglycaemic range seen in the present study and not only in subjects with diabetes mellitus.…”

Calcium and diabetic vascular dysfunction. Focus on “Elevated Ca2+ sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells”

“…Barbagallo et al (1) reported that glucose induces a concentration-dependent increase in global intracellular calcium concentration ([Ca 2ϩ ] i ) in cultured rat tail vascular smooth muscle (VSM) cells, and elevated cytosolic [Ca 2ϩ ] has also been observed in diabetic rodent models (1,14). The nature and characteristics of the Ca 2ϩ signal responsible for the increase in [Ca 2ϩ ] i in diabetes has not been determined; however, several lines of evidence have suggested that Ca 2ϩ entry through L-type Ca 2ϩ channels in VSM cell plasma membranes may play a role (11).…”