Increased cytochrome P4502E1 expression and altered hydroxyeicosatetraenoic acid formation mediate diabetic vascular dysfunction: rescue by guanylyl-cyclase activation.

Objective: We investigated the mechanisms underlying vascular endothelial and contractile dysfunction in diabetes as well as the effect of HMR1766, a novel nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC).

Research Design And Methods: Two weeks after induction of diabetes by streptozotocin, Wistar rats received either placebo or HMR1766 (10 mg/kg twice daily) for another 2 weeks; thereafter, vascular function was assessed.

Results: Endothelial function and contractile responses were significantly impaired, while vascular superoxide formation was increased in the aortae from diabetic versus healthy control rats.

Characterization of a novel interaction between vasodilator-stimulated phosphoprotein and Abelson interactor 1 in human platelets: a concerted computational and experimental approach.

Objective: The goal of this study was systematic profiling of vasodilator-stimulated phosphoprotein (VASP)-Ena/VASP homology 1 (EVH1) interactors in human platelets using a combined in silico and in vitro approach.

Methods And Results: Exploiting the information of the comprehensive proteome catalogue in the PlateletWeb database (http://plateletweb.bioapps.

Telmisartan improves vascular function and reduces platelet activation in rats with streptozotocin-induced diabetes mellitus.

Diabetes is associated with vascular dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. We investigated whether the angiotensin II antagonist telmisartan improves vascular dysfunction and reduces platelet activation in diabetic rats. Therefore, male Wistar rats were injected with streptozotocin (50 mg kg(-1) i.

Volatile anesthetics affect the morphology of rat glioma C6 cells via RhoA, ERK, and Akt activation.

Treatment of rat glioma C6 cells with the beta-receptor agonist isoproterenol induces a massive increase in cAMP. Concomitantly the cells change their morphology from a fibroblast-type to an astrocyte-like (stellated) cell shape. The stellated morphology can be completely reverted by thrombin and sphingosine-1-phosphate (S-1-P) but also to a certain extent by clinical concentrations of volatile anesthetics.

Improved endothelial function and reduced platelet activation by chronic HMG-CoA-reductase inhibition with rosuvastatin in rats with streptozotocin-induced diabetes mellitus.

Diabetes is associated with endothelial dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. We investigated whether the hydroxy-3-methyl-glutaryl CoA reductase inhibitor rosuvastatin improves endothelial function and reduces platelet activation in diabetic rats. Therefore, male Wistar rats were injected with streptozotocin (STZ, 50mg/kg i.

The CX3C chemokine fractalkine induces vascular dysfunction by generation of superoxide anions.

Objective: The chemokine fractalkine activates platelets and induces leukocyte adhesion to the endothelium. Expression of fractalkine and its receptor, CX3CR1, is elevated in coronary artery disease. We assessed the effects of fractalkine on vascular function in isolated rat aorta.

Halothane inhibits spontaneous calcium oscillations via adenosine A1 receptors.

Primary rat hippocampal neurons show spontaneous [Ca(2+)(i)]-oscillations in Mg(2+)-free medium, which depend on excitatory signal transmission by N-methyl-D-aspartate /[alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors modulated by inhibitory [gamma]-amino-n-butyric acid type A receptors. Volatile anesthetics depress these oscillations by potentiating the inhibitory action of [gamma]-amino-n-butyric acid type A receptors, and as shown recently, indirectly by activation of adenosine A1-receptors. The purpose of this investigation was to study whether inactivation of adenosine A1-receptors can prevent the anesthetic-induced inhibition.

Regulation of aldosterone production from zona glomerulosa cells by ANG II and cAMP: evidence for PKA-independent activation of CaMK by cAMP.

Aldosterone production in zona glomerulosa (ZG) cells of adrenal glands is regulated by various extracellular stimuli (K(+), ANG II, ACTH) that all converge on two major intracellular signaling pathways: an increase in cAMP production and calcium (Ca(2+)) mobilization. However, molecular events downstream of the increase in intracellular cAMP and Ca(2+) content are controversial and far from being completely resolved. Here, we found that Ca(2+)/calmodulin-dependent protein kinases (CaMKs) play a predominant role in the regulation of aldosterone production stimulated by ANG II, ACTH, and cAMP.

Rosuvastatin reduces platelet activation in heart failure: role of NO bioavailability.

Objectives: Endothelial dysfunction and platelet activation are part of the cardiovascular phenotype in congestive heart failure (CHF). We investigated whether 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibition would beneficially modulate vascular NO bioavailability and platelet activation in experimental CHF.

Methods And Results: Chronic myocardial infarction was induced by coronary ligation in male Wistar rats.

Vascular endothelial dysfunction and superoxide anion production in heart failure are p38 MAP kinase-dependent.

Objective: The mitogen-activated protein (MAP) kinase system, especially the p38 MAP kinase, is activated in chronic heart failure (CHF). However, the role of vascular p38 MAP kinase in CHF has not been analyzed yet.

Methods And Results: In aortic rings from rats with CHF 10 weeks after myocardial infarction, acetylcholine-induced relaxation was attenuated (maximum relaxation, Rmax: 54+/-5%) compared to sham-operated animals (Rmax: 77+/-5%, p<0.

Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism.

Background: Endothelial dysfunction of the vasculature contributes to the elevated peripheral resistance and reduced myocardial perfusion in congestive heart failure (CHF). The present study systematically investigated the effect of angiotensin II (AT(1))- receptor blockade on vascular superoxide (O(2)(-)) production and endothelial dysfunction.

Methods And Results: Vasodilator responses and O(2)(-) production were determined in aortic rings from Wistar rats with experimental CHF 10 weeks after extensive myocardial infarction and compared with sham-operated animals (Sham).

The volatile anesthetic isoflurane inhibits the histamine-induced Ca2+ influx in primary human endothelial cells.

Unlabelled: Although isoflurane is a known vasodilator, the mechanism of isoflurane-induced vasodilation is not clear. One of the most important systems in this context is the nitric oxide (NO)-mediated vasodilation. The activity of this system is regulated by the agonist-induced Ca(2+) influx rather than Ca(2+) release from internal stores.

Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction.

Objectives: To investigate the effects of adding the selective aldosterone receptor antagonist eplerenone to ACE inhibition on endothelium-dependent vasodilation in rats with chronic heart failure (CHF).

Background: Addition of the non-selective aldosterone antagonist spironolactone to ACE-inhibitors reduces mortality and morbidity in CHF and improves endothelial vasomotor dysfunction, but is associated with considerable side-effects.

Methods: Starting 10 days after extensive myocardial infarction (MI) or sham-operation, Wistar rats were treated either with placebo, the ACE inhibitor trandolapril (TR, 0.

Phorbol Ester Interferes with [3H]Norepinephrine Accumulation into Monolayers of PC 12 Cells by Stimulating the Release of Endogenous Norepinephrine.

In this study we have observed an inhibition of the [3H]norepinephrine ([3H]NE) accumulation into rat phaeochromocytoma PC 12 cells by phorbol 12-myristate 13-acetate (PMA), whereas a biologically inactive phorbol ester was without effect. The inhibition was no longer observed when the PC 12 cells were preincubated with 10 microM reserpine, which inhibits the uptake of norepinephrine into the storage vesicles. This suggested a role of the intact vesicles in the inhibitory phenomenon.