Biomedical subjects

Koen Boussery

Publications and source records attributed to Koen Boussery.

9 recordsLinked to original sources

PubMed2005

Clozapine directly relaxes bovine retinal arteries.

PURPOSE: It was suggested that clozapine might be helpful in the development of new antiglaucoma agents, as it combines lowering the intraocular pressure after topical instillation with vasodilation. This study aimed to evaluate and characterize the vasodilatory effect of clozapine in isolated bovine retinal arteries (BRAs). METHODS: Retinal arteries were isolated from bovine eyes and mounted in the organ bath of a small vessel myograph. RESULTS: Cumulative addition of clozapine (1 nM to 10 microM) caused a concentration-dependent relaxation of the BRAs. Removal of the endothelium, inhibition of nitric oxide synthase and of soluble guanylyl cyclase reduced the clozapine response, whereas cyclooxygenase inhibition had no influence. A Ca2+ channel activator, a 5-hydroxytryptamine receptor antagonist, and an adenosine receptor antagonist failed in affecting the clozapine-induced relaxations. CONCLUSIONS: Clozapine relaxes bovine retinal arteries. Endothelium-derived NO seems to be involved, whereas prostanoids, calcium entry blockade, 5-HT7 receptor stimulation, and adenosine receptor stimulation do not.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2005

The vasorelaxing effect of CGRP and natriuretic peptides in isolated bovine retinal arteries.

PURPOSE: To study the vasorelaxing effect of calcitonin gene-related peptide (CGRP) and natriuretic peptides on isolated bovine retinal arteries (BRAs) and to evaluate the possibility of the unidentified retinal relaxing factor (RRF) being one of these peptides. METHODS: Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of the peptides to the organ bath. RESULTS: In BRAs, CGRP-induced relaxation was significantly reduced by removal of the endothelium or by application of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine (l-NA) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The nonselective K(+) channel blocker tetraethylammoniumchloride (TEA) and the voltage-dependent K(+) channel blocker 4-aminopyridine significantly reduced the CGRP response, whereas the Ca(2+) activated K(+) channel blockers apamin plus charybdotoxin, the inward rectifier K(+) channel blocker Ba(2+), and the adenosine triphosphate (ATP)-sensitive K(+) channel blocker glibenclamide had no effect. The CGRP receptor antagonist CGRP 8-37 caused a small, but not significant, rightward shift in the concentration-response curve for CGRP, whereas the AM-receptor antagonist AM 22-52 had no effect. The natriuretic peptides did not induce relaxation in isolated retinal arteries. CONCLUSIONS: Endothelium-derived NO, voltage-dependent K(+) channels, and possibly also CGRP(1) receptors are involved in the CGRP response in BRAs. The natriuretic peptides do not induce vasorelaxation in isolated BRAs. No evidence was found that CGRP or a natriuretic peptide is the as yet unidentified RRF.

Animals↗

PubMed2005

Vitreous: a barrier to nonviral ocular gene therapy.

PURPOSE: Intravitreal injection of therapeutic DNA, complexed to nonviral carriers such as cationic liposomes, may be promising in the treatment of many severe retinal eye diseases. However, after intravitreal injection, such DNA/cationic liposome complexes-called lipoplexes (LPXs)-which are typically hundreds of nanometers in size, must first diffuse through the vitreous before they can reach the retina. The aim of this study was to elucidate whether vitreous is a barrier for the LPXs and to find strategies to overcome this barrier. METHODS: Fluorescent polystyrene nanospheres and LPXs were mixed with vitreous, and their mobility was monitored by fluorescence recovery after photobleaching (FRAP), a microscopy-based technique. The stability of LPXs and naked plasmid DNA in vitreous was studied by gel electrophoresis. RESULTS: We showed that polystyrene nanospheres, in our first experiments used as a model for the LPXs, do not diffuse freely into the vitreous but adhere to fibrillar structures in the vitreous, most likely to collagen fibers. Making the surfaces of the polystyrene nanospheres hydrophilic by attaching hydrophilic polyethylene glycol (PEG) chains at their surfaces circumvented the binding to fibrillar structures in the vitreous. FRAP revealed that "pegylated" polystyrene nanospheres, as long as they are smaller than 500 nm, are indeed mobile in the vitreous. It was further demonstrated that LPXs severely aggregate in vitreous and strongly bind to biopolymers in the vitreous, which immobilizes them completely. However, as observed for the polystyrene nanospheres, coating of the LPXs with PEG averted their aggregation in the vitreous and their binding to fibrillar structures. CONCLUSIONS: Modifying the surfaces of LPXs with hydrophilic PEG chains prevents them from aggregating in vitreous. In this way, LPXs are obtained that can freely move in vitreous, an absolute criterion for reaching the retina after intravitreal injection.

Animals↗

PubMed2005

Hyperosmolarity increases K+-induced vasodilations in rat skeletal muscle arterioles.

PURPOSE: Exercise hyperemia is mediated by a multitude of vasoactive metabolites released from the active skeletal muscle. Because several vasoactive factors might interact during the hyperemia response, we investigated the influence of hyperosmolarity (HO) on K(+)-induced relaxations. METHODS: Small gluteal rat arteries (diameter: 245 +/- 6 microm) were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, 1, 2, or 3 mM K(+) was added in both control, moderate, or high hyperosmotic (30 mM (S30) or 60 mM sucrose (S60)) conditions. Endothelial removal and the addition of ouabain, Ba(2+), 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), or glibenclamide was used to study the underlying mechanisms. RESULTS: The K(+)-induced relaxations were significantly (P < 0.001) increased in the presence of S30 and S60. Endothelial removal and the addition of glibenclamide or ouabain did not reduce the HO-induced increased sensitivity to K(+). The application of Ba abolished the influence of HO on the K(+)-induced relaxations. NPPB, a volume regulated anion channel (VRAC) blocker, mimicked the influence of HO by significantly (P < 0.05) increasing the K(+)-induced relaxations. Remarkably, the application of Ba(2+) abolished the sensitizing effect of NPPB on K(+)-induced relaxations. CONCLUSION: HO increases the sensitivity of the rat gluteal skeletal muscle arteries to the vasodilating effect of K(+). It is hypothesized that HO inhibits VRAC causing smooth muscle hyperpolarization. This possibly sensitizes the K(ir)-channels that are known to be involved in the K-induced relaxations in this type of arteries.

Animals↗

PubMed2004

Influence of adrenomedullin on tone of isolated bovine retinal arteries.

PURPOSE: To assess and characterize the vasorelaxing effect of adrenomedullin (AM) on isolated bovine retinal arteries (BRAs). METHODS: Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of AM (1 pM to 0.1 micro M) to the organ bath. RESULTS: AM caused a concentration-dependent relaxation of the BRAs. Removal of the endothelium of the BRAs, inhibition of nitric oxide synthase with -nitro-L-arginine (L-NA) or inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly reduced the AM response. Cyclooxygenase inhibition with indomethacin or sodium diclofenac did not reduce, but rather increased, vasodilation. The AM-receptor antagonist AM 22-52 slightly, but significantly, reduced the AM response, whereas the CGRP-receptor antagonist CGRP 8-37 caused a more pronounced reduction. The adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (8-SPT) did not affect AM-induced vasorelaxation. Inhibition of several intracellular calcium ([Ca(2+)](i))-reducing mechanisms failed to block the relaxation induced by AM. Only inhibition of the plasma membrane Ca(2+)-adenosine triphosphatase (ATPase) with vanadate significantly attenuated the AM response. CONCLUSIONS: AM induces vasodilation in isolated bovine retinal arteries. Endothelium-derived NO and stimulation of CGRP- and AM-receptors appear to be involved in the AM response, whereas prostanoids and activation of adenosine receptors are not involved. Activation of Ca(2+)-extrusion by the plasma membrane Ca(2+)-ATPase may elicit the relaxation of BRAs in response to AM.

Adrenomedullin↗

PubMed2003

Potassium potently relaxes small rat skeletal muscle arteries.

INTRODUCTION: Skeletal muscle contraction elicits an explosive rise in interstitial potassium (K+) concentration. K+ has been considered as one of the most potent vasoactive metabolites in skeletal muscle arterioles. Studies on isolated blood vessels report large relaxations when extracellular [K+] is increased up to 10 mM. We studied the effects of smaller and physiologically more relevant increases in [K+] (adding 1, 2, and 3 mM) and compared them with relaxations induced by the endothelium derived hyperpolarizing factor (EDHF). METHODS: Rat gluteal arteries were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, acetylcholine or K+ was added in control conditions, after removal of the endothelium or in the presence of ouabain or Ba2+. RESULTS: Application of 1, 2, or 3 mM K+ induced large vasodilations (up to 75.4% with 3 mM) (N = 40), which were more sustained at the higher concentrations. Removal of the vascular endothelium had no effect on this relaxation. Inhibition of the Kir channels with Ba2+ did not alter the K+-induced relaxations, although it significantly inhibited the EDHF-mediated relaxation. Incubation with ouabain significantly decreased the K+- and EDHF-induced relaxation. Simultaneous application of Ba2+ and ouabain totally abolished both K+- and EDHF-induced responses. CONCLUSION: Even small increases in extracellular K+ concentration elicit large endothelium-independent and ouabain-sensitive relaxations in small skeletal muscle arteries. The fact that both K+- and EDHF-induced vasorelaxations show similar characteristics indicates that K+ might be the EDHF in this type of artery.

Animals↗

PubMed2002

Vasorelaxing effect of mesaconitine, an alkaloid from Aconitum japonicum, on rat small gastric artery: possible involvement of endothelium-derived hyperpolarizing factor.

Aconiti tuber, roots of aconite (Aconitum japonicum), has been used for centuries in Japan and China to increase peripheral body temperature. We previously reported that mesaconitine, an alkaloid from Aconitum japonicum, elicits endothelium-dependent and nitric oxide-mediated relaxation in isolated rat aorta. In the present study, we investigated the effect of mesaconitine on isolated rat small gastric arteries. Mesaconitine elicited a concentration-dependent (10, 30, 100 microM) vasorelaxation in isolated rat gastric artery precontracted with norepinephrine, which was resistant to N(omega)-nitro-L-arginine (L-NNA) (an inhibitor of nitric oxide synthase) and indomethacin (an inhibitor of cyclooxygenase). The L-NNA- and indomethacin-resistant relaxation by mesaconitine was mainly endothelium-dependent, inhibited by high K+ (30 mM), and inhibited by a combination of Ca2+-dependent K channel blockers, charybdotoxin and apamin. The relaxation by mesaconitine was proportional to the external Ca2+ concentration. These results suggest that mesaconitine elicits vasorelaxation of isolated rat small gastric artery mainly via release of endothelium-derived hyperpolarizing factor.

Aconitine↗

PubMed2002

Rat retinal tissue releases a vasorelaxing factor.

PURPOSE: To investigate whether the retina of the rat exerts a vasodilatory influence by the release of a relaxing factor and to characterize the retinal relaxing factor (RRF). METHODS: The relaxing influence of the rat retina was investigated by placing the retina in close proximity with a precontracted isolated rat carotid artery ring segment, mounted for isometric tension measurements. RESULTS: Application of rat retina relaxed the artery in a reliable and reproducible way. The nitric oxide (NO)-synthase inhibitor N(omega)-nitro-L-arginine (L-NA), the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and the removal of the endothelium of the artery all failed to affect the RRF response. The RRF response was not decreased; in contrast, it increased after treatment with a cyclooxygenase (COX) inhibitor (indomethacin or sodium diclofenac). Acute hypoxia largely enhanced retina-induced relaxation. Several potential mediators of hypoxia-induced vasodilation were excluded as candidates for the RRF or for mediating the enhanced response to RRF in hypoxia. Inhibition of the plasma membrane Ca(2+)-adenosine triphosphatase (ATPase) with vanadate significantly affected the RRF response. CONCLUSIONS: The release of an as yet unidentified relaxing factor(s) from the rat retina was demonstrated. Acute hypoxia profoundly enhances the RRF response. None of the known mediators of hypoxia-induced vasodilation nor NO, prostanoids, or endothelial factors mediate the RRF response. Activation of the plasma membrane Ca(2+)-ATPase seems to be involved in the RRF response.

Acute Disease↗

PubMedDate not supplied

A vasorelaxing factor is released from mouse retinal tissue.

The present study aimed to demonstrate the release of a retinal relaxing factor (RRF) from the retina of mice and to investigate the identity of the RRF. Ring segments of a mouse aorta were mounted in a small vessel myograph. The relaxing influence of mouse retinal tissue was assessed by placing a retina in close proximity to the precontracted aorta. This elicited reliable and reproducible relaxations in the aorta. Both the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine and the soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one had no effect on the RRF response. Also the cyclooxygenase inhibitors indomethacin and sodium diclofenac failed to affect the retina-induced relaxations. Acute hypoxia largely enhanced retina-induced relaxations. It is concluded that mouse retinal tissue releases an RRF, that the mouse RRF response is not mediated by NO or prostanoids and that the mouse RRF response is profoundly influenced by hypoxia.

Acute Disease↗