<i>Calcium and diabetic vascular dysfunction</i>. Focus on “Elevated Ca<sup>2+</sup> sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells”

Dunn, Kathryn M.; Nelson, Mark T.

doi:10.1152/ajpcell.00499.2009

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…Moreover, smooth muscle cells (Ca 2+ ) have the potential to significantly impair normal physiological function of the vascular system [27]. Vasoconstriction is induced by different materials involved in different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…One of the pathogenesis of diabetic vascular dysfunction is oxygen derived free radicals, which are significantly elevated under DM [24–26]. Diabetic vascular dysfunction is also related to increased Ca 2+ influx [27] and inhibited vascular K + channels [28]. Previous studies showed that the inhibition of vascular K + channels increases Ca 2+ influx, which leads to depolarization and vasoconstriction [28].…”

Section: Introductionmentioning

confidence: 99%

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Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

et al. 2012

IJMS

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One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl2-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic groups compared with those in diabetic and Pae-treated diabetic groups. In addition, superoxide dismutase activity and thiobarbituric acid reactive substances content significantly changed in the presence of Pae + DSS. We therefore conclude that both Pae and DSS treatments prevent diabetes-induced vascular damage. Furthermore, Pae + DSS prove to be the most efficient treatment regimen. The combination of Pae and DSS produce significant protective effects through the reduction of oxidative stress and through intracellular Ca2+ regulatory mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

et al. 2012

IJMS

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“…However, few of these treatments have been designed to directly recover the vascular dysfunction in diabetes. Because the elevated concentration of intracellular Ca 2+ ([Ca 2+ ] i ) is the primary stimulus for smooth muscle contraction, it is reported that diabetic vascular dysfunction is tightly coupled to the impairment of intracellular Ca 2+ handling in vascular smooth muscle cells (VSMCs) [ 3 , 4 ]. Ca 2+ influx from the long-lasting voltage-dependent Ca 2+ (L-type, Ca L ) channels in plasma membrane and Ca 2+ releases from the ryanodine receptors (RyRs) in sarcoplasmic reticulum (SR) are the key factors to regulate the intracellular Ca 2+ in VSMCs [ 3 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca2+ handling in smooth muscle cells

Zhang

Bai

et al. 2016

Cardiovasc Diabetol

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BackgroundVascular dysfunction is a distinctive phenotype in diabetes mellitus. Current treatments mostly focus on the tight glycemic control and few of these treatments have been designed to directly recover the vascular dysfunction in diabetes. As a classical natural medicine, berberine has been explored as a possible therapy for DM. In addition, it is reported that berberine has an extra-protective effect in diabetic vascular dysfunction. However, little is known whether the berberine treatment could ameliorate the smooth muscle contractility independent of a functional endothelium under hyperglycemia. Furthermore, it remains unknown whether berberine affects the arterial contractility by regulating the intracellular Ca2+ handling in vascular smooth cells (VSMCs) under hyperglycemia.MethodsSprague–Dawley rats were used to establish the diabetic model with a high-fat diet plus injections of streptozotocin (STZ). Berberine (50, 100, and 200 mg/kg/day) were intragastrically administered to control and diabetic rats for 8 weeks since the injection of STZ. The intracellular Ca2+ handling of isolated cerebral VSMCs was investigated by recording the whole-cell L-type Ca2+ channel (CaL) currents, assessing the protein expressions of CaL channel, and measuring the intracellular Ca2+ in response to caffeine. Our results showed that chronic administration of 100 mg/kg/day berberine not only reduced glucose levels, but also inhibited the augmented contractile function of cerebral artery to KCl and 5-hydroxytryptamine (5-HT) in diabetic rats. Furthermore, chronic administration of 100 mg/kg/day berberine significantly inhibited the CaL channel current densities, reduced the α1C-subunit expressions of CaL channel, decreased the resting intracellular Ca2+ ([Ca2+]i) level, and suppressed the Ca2+ releases from RyRs in cerebral VSMCs isolated from diabetic rats. Correspondingly, acute application of 10 μM berberine could directly inhibit the hyperglycemia-induced CaL currents and suppress the hyperglycemia-induced Ca2+ releases from RyRs in cerebral VSMCs isolated from normal control rats.ConclusionsOur study indicated that berberine alleviated the cerebral arterial contractility in the rat model of streptozotocin-induced diabetes via regulating the intracellular Ca2+ handling of smooth muscle cells.

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“…While the majority of research effort concerning diabetic vascular disease has been focused on changes in the endothelial cells, alterations in the vascular smooth muscle cells (VSMCs) are also known to occur [11-13]. The VSMCs surrounding vessel walls, undergo increased proliferation, adhesion, and migration in conditions of hyperglycemia [14-17].…”

Section: Introductionmentioning

confidence: 99%

Intracellular Ca2+ regulating proteins in vascular smooth muscle cells are altered with type 1 diabetes due to the direct effects of hyperglycemia

Searls

Loganathan

Smirnova

et al. 2010

Cardiovasc Diabetol

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BackgroundDiminished calcium (Ca2+) transients in response to physiological agonists have been reported in vascular smooth muscle cells (VSMCs) from diabetic animals. However, the mechanism responsible was unclear.Methodology/Principal FindingsVSMCs from autoimmune type 1 Diabetes Resistant Bio-Breeding (DR-BB) rats and streptozotocin-induced rats were examined for levels and distribution of inositol trisphosphate receptors (IP3R) and the SR Ca2+ pumps (SERCA 2 and 3). Generally, a decrease in IP3R levels and dramatic increase in ryanodine receptor (RyR) levels were noted in the aortic samples from diabetic animals. Redistribution of the specific IP3R subtypes was dependent on the rat model. SERCA 2 was redistributed to a peri-nuclear pattern that was more prominent in the DR-BB diabetic rat aorta than the STZ diabetic rat. The free intracellular Ca2+ in freshly dispersed VSMCs from control and diabetic animals was monitored using ratiometric Ca2+ sensitive fluorophores viewed by confocal microscopy. In control VSMCs, basal fluorescence levels were significantly higher in the nucleus relative to the cytoplasm, while in diabetic VSMCs they were essentially the same. Vasopressin induced a predictable increase in free intracellular Ca2+ in the VSMCs from control rats with a prolonged and significantly blunted response in the diabetic VSMCs. A slow rise in free intracellular Ca2+ in response to thapsigargin, a specific blocker of SERCA was seen in the control VSMCs but was significantly delayed and prolonged in cells from diabetic rats. To determine whether the changes were due to the direct effects of hyperglycemica, experiments were repeated using cultured rat aortic smooth muscle cells (A7r5) grown in hyperglycemic and control conditions. In general, they demonstrated the same changes in protein levels and distribution as well as the blunted Ca2+ responses to vasopressin and thapsigargin as noted in the cells from diabetic animals.Conclusions/SignificanceThis work demonstrates that the previously-reported reduced Ca2+ signaling in VSMCs from diabetic animals is related to decreases and/or redistribution in the IP3R Ca2+ channels and SERCA proteins. These changes can be duplicated in culture with high glucose levels.

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

Cited by 10 publications

References 18 publications

Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca2+ handling in smooth muscle cells

Intracellular Ca2+ regulating proteins in vascular smooth muscle cells are altered with type 1 diabetes due to the direct effects of hyperglycemia

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

Cited by 10 publications

References 18 publications

Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca2+ handling in smooth muscle cells

Intracellular Ca2+ regulating proteins in vascular smooth muscle cells are altered with type 1 diabetes due to the direct effects of hyperglycemia

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