Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.

Williams, Bryan; Tsai, Pei‐San; Schrier, Robert W.

doi:10.1172/jci116079

Cited by 65 publications

(32 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This mechanism is also consistent with the failure of glucose washout over the course of an hour to significantly lower glucose-induced elevated Cai levels. A second potential mechanism for the observed glucose effects involves glucose-induced stimulation of diacylglycerol formation and protein kinase C activity (28)(29)(30), potentially recruiting calcium from intracellular storage sites via IP3 formation. The fact that glucose has similar calcium-stimulating effects in the red cell, devoid of intracellular organelles, makes this mechanism less likely.…”

Section: Discussionmentioning

confidence: 99%

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

Barbagallo¹,

Shan²,

Pang³

et al. 1995

J. Clin. Invest.

View full text Add to dashboard Cite

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.)

show abstract

Section: Discussionmentioning

confidence: 99%

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

Barbagallo¹,

Shan²,

Pang³

et al. 1995

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…With regard to diabetes mellitus, more recent studies have shown that the PKC inhibitor staurosporine can restore to normal the previously elevated leucocyte Na+/H+ antiport activity ofdiabetic patients, thereby suggesting that diabetes-induced increases in Na+/H+ antiport activity may be dependent on PKC activation (19). Diabetes mellitus is characterized by the development of hyperglycemia, and we have recently shown that elevated extracellular glucose concentrations (20 mM) induce a sustained activation of PKC in cultured VSMC (20,21 ). Together, these observations prompt the hypothesis that metabolic factors, in particular, hyperglycemia could directly influence the activity of the Na+/H+ antiport in the vasculature ofdiabetic patients via glucose-induced activation ofPKC.…”

Section: Introductionmentioning

confidence: 92%

Glucose-induced changes in Na+/H+ antiport activity and gene expression in cultured vascular smooth muscle cells. Role of protein kinase C.

Williams

Howard²

1994

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

Increased Na/ H antiport activity has been implicated in the pathogenesis of hypertension and vascular disease in diabetes mellitus. The independent effect of elevated extracellular glucose concentrations on Na+/H+ antiport activity in cultured rat vascular smooth muscle cells (VSMC) was thus examined. Amiloride-sensitive 22Na' uptake by VSMC significantly increased twofold after 3 and 24 h of exposure to high glucose medium (20 mM) vs. control medium (5 mM). Direct glucoseinduced Na+/ H+ antiport activation was confirmed by measuring Na '-dependent intracellular pH recovery from intracellular acidosis. High glucose significantly increased protein kinase C (PKC) activity in VSMC and inhibition of PKC activation with H-7, staurosporine, or prior PKC downregulation prevented glucose-induced increases in Na+/H+ antiport activity in VSMC. Northern analysis of VSMC poly A' RNA revealed that high glucose induced a threefold increase in Na+/H+ antiport (NHE-1) mRNA at 24 h. Inhibiting this increase in NHE-1 mRNA with actinomycin D prevented the sustained glucoseinduced increase in Na+/H+ antiport activity. In conclusion, elevated glucose concentrations significantly influence vascular Na+/H+ antiport activity via glucose-induced PKC dependent mechanisms, thereby providing a biochemical basis for increased Na+/H+ antiport activity in the vascular tissues of patients with hypertension and diabetes mellitus. (J. Clin. Invest. 1994. 93:2623-2631

show abstract

“…Importantly, such a reduction in the number of receptors could affect agonist-induced responses/function in cells, leading to the observed impairments of [Ca 2+ ] i responses and NO production upon bradykinin stimulation. Indeed, a 33% reduction in the number of receptors due to PKC activation induced a proportional decrease of bradykinin-mediated IP 3 formation in fibroblasts [21], and a 40% down-regulation of arginine vasopressin receptors in high-glucose-cultured vascular smooth muscle cells resulted in a similar extent of inhibition of arginine-vasopressin-induced [Ca 2+ ] i elevations [43]. Whether high glucose is also able to reduce the number of other receptors (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Earlier studies showed that acute PKC activation has a negative feedback effect on the pathway linking receptors to PLC stimulation [43,44,45]. Furthermore, PKC (especially β and δ isoforms) is excessively activated in high glucose environments due to enhanced de novo synthesis of diacylglycerol [12,32,33].…”

Section: Discussionmentioning

confidence: 99%

“…This notion is also applicable to the reduction in the number of bradykinin receptors under the same conditions. Similarly, the PKC inhibitor reversed high-glucose-induced down-regulation of the numbers of angiotensin II and arginine vasopressin receptors in vascular smooth muscle cells [43]. How PKC activation causes receptor down-regulation is unclear, but one possibility is through the suppression of mRNA expression [46].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C

Tang

2004

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. Overwhelming evidence indicates that endothelial cell dysfunction in diabetes is characterised by diminished endothelium-dependent relaxation, but the matter of the underlying molecular mechanism remains unclear. As nitric oxide (NO) production from the endothelium is the major player in endothelium-mediated vascular relaxation, we investigated the effects of high glucose on NO production, and the possible alterations of signalling pathways implicated in this scenario. Methods. NO production and intracellular Ca 2+ levels ([Ca 2+ ] i ) were assessed using the fluorescent probes 4,5-diaminofluorescein diacetate and fura-2 respectively. Results. Exposure of cultured bovine aortic endothelial cells to high glucose for 5 or 10 days significantly reduced NO production induced by bradykinin (but not by Ca 2+ ionophore) in a time-and dose-dependent manner. This was probably due to an attenuation in bradykinin-induced elevations of [Ca 2+ ] i under these conditions, since a close correlation between [Ca 2+ ] i increases and NO generation was observed in intact bovine aortic endothelial cells. Both bradykinin-promoted intracellular Ca 2+ mobilisation and extracellular Ca 2+ entry were affected. Moreover, bradykinin-induced formation of Ins(1,4,5)P 3 , a phospholipase C product leading to increases in [Ca 2+ ] i , was also inhibited following high glucose culture. This abnormality was not attributable to a decrease in inositol phospholipids, but possibly to a reduction in the number of bradykinin receptors. The alterations in NO production, the increases in [Ca 2+ ] i , and the bradykinin receptor number due to high glucose could be largely reversed by protein kinase C inhibitors and D-α-tocopherol (antioxidant). Conclusions/interpretation. Chronic exposure to high glucose reduces NO generation in endothelial cells, probably by impairing phospholipase-C-mediated Ca 2+ signalling due to excess protein kinase C activation. This defect in NO release may contribute to the diminished endothelium-dependent relaxation and thus to the development of cardiovascular diseases in diabetes.

show abstract

Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.

Abstract: Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II

Cited by 65 publications

References 50 publications

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

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

Glucose-induced changes in Na+/H+ antiport activity and gene expression in cultured vascular smooth muscle cells. Role of protein kinase C.

Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C

Contact Info

Product

Resources

About