Perivascular Expression and Potent Vasoconstrictor Effect of Dynorphin A in Cerebral Arteries

BACKGROUND: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K(+), were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 µM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of G(i/o)-protein mediated signaling by pertussis toxin. Finally, des-Tyr(1) DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 µM, which effects were resistant to NORBI. CONCLUSION/SIGNIFICANCE: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric G(i/o)-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors

Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

BACKGROUND AND PURPOSE: Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. METHODS: Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. RESULTS: VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. CONCLUSIONS: VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD

Editorial: Special Section on Biological Medical Systems

[No abstract available

The roleS of ABA, reactive oxygen species and Nitric Oxide in root growth during osmotic stress in wheat: comparison of a tolerant and a sensitive variety

The effects of PEG 6000-induced osmotic stress (−0.976 MPa) on the root growth of young plants, and the changes in abscisic acid (ABA), reactive oxygen species (ROS) and NO contents were investigated in the root tips of a drought-tolerant and a drought-sensitive wheat cultivar (Triticum aestivum L. cvs. MV Emese and GK Élet, respectively). The root length of cv. MV Emese was more effectively reduced than that of GK Élet by osmotic stress. Concomitantly, the ABA content of the 15-mm apical zone of the roots remained at the control level in GK Élet cultivar, but in MV Emese it decreased significantly after the early phase of the experiment, indicating that the accumulation of ABA is necessary for the maintenance of root growth under osmotic stress. The extent of ROS accumulation relative to the respective control was more pronounced in the elongation zone of roots in MV Emese in the later stages of the experiment, while NO concentrations increased significantly early after PEG exposure, suggesting that high concentrations of ROS and NO were unfavourable for root expansion. In contrast, in cv. Élet, the high NO content in the elongation zone declined to the control level under osmotic stress within 4 days. The changes in root growth due to osmotic stress did not exhibit a correlation with the drought tolerance of the genotypes defined on the basis of the crop yield

An enhanced method for accessory pathway localization in case of Wolff-Parkinson-White syndrome

This paper presents an analysis of the Arruda accessory pathway localization method for patients suffering from Wolff-Parkinson-White syndrome, with modifications to increase the overall accuracy. The Arruda method was tested on a total of 79 cases, and 91.1% localization performance was reached. After a deeper analysis of each decision point of the Arruda localization method, we considered that the lead aVF was not as relevant as other leads (I, II, III, V1) used. The branch of the decision tree, which evaluates the left ventricle positions, was entirely replaced using different decision criteria based on the same biological parameters. The modified algorithm significantly improves the localization accuracy in the left ventricle, reaching 94.9%. An accurate localization performance of non-invasive methods is relevant because it can enlighten the necessary invasive interventions, and it also reduces the discomfort caused to the patient