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J Van de Voorde

Publications and source records attributed to J Van de Voorde.

At least 19 recordsLinked to original sources
PubMed2002

Contractility studies on isolated bovine choroidal small arteries: determination of the active and passive wall tension-internal circumference relation.

Studies on isolated choroidal arteries could help to understand the regulatory mechanisms in the choroidal circulation. The aim of the present study was therefore to assess whether contractility studies on isolated choroidal arteries were feasible and to determine the active and passive wall tension-internal circumference relation of these arteries. This relation is essential for reliable further pharmacodynamic studies on these vessels. Isolated choroidal arteries were mounted on a wire myograph for isometric tension recording. After the vessel was mounted, the L(100) (the circumference of the vessel at a transmural pressure of 100 mmHg) was determined. Then the passive and active wall tension-internal circumference relation of the choroidal vessels was obtained by stepwise increasing the internal circumference. The changes in the internal circumference were expressed as a percentage of L(100). After each increase in circumference, the passive tone (in a calcium free medium), the spontaneous tone (in a Krebs--Ringer bicarbonate solution) and the active tone (in a solution containing K(+) 120 mM and prostaglandin F(2 alpha) 30 microM) was measured. The passive tone of the vessel increased exponentially with the circumference of the vessel. Both the spontaneous tone and the active tone also increased when the vessel was stretched. They peaked when the internal circumference approached 90% of the L(100) and diminished again when the circumference was further increased. The peak value of the active tension curve averaged 2.24+/-0.47 Nm(-1) (n=10). The passive tension was 0.57+/-0.08 Nm(-1) (n=10) at this circumference. The peak value of the spontaneous tension curve averaged 0.37+/-0.08 Nm(-1) (n=10). It can be concluded that in vitro contractility studies on isolated choroidal arteries are feasible. The optimal length or preload of the choroidal arteries is attained when the internal circumference of the artery is set to 90% of the L(100).

Animals↗
PubMed2001

Regional differences in anandamide- and methanandamide-induced membrane potential changes in rat mesenteric arteries.

The possibility that anandamide is an endothelium-derived hyperpolarizing factor was explored in the rat mesenteric vasculature by use of conventional microelectrode techniques. In the main mesenteric artery, anandamide and its more stable analog methanandamide hardly caused a measurable change in membrane potential of the smooth muscle cells, which promptly hyperpolarized to EDHF liberated by acetylcholine. Inhibition of endogenous anandamide breakdown by phenylmethylsulfonyl fluoride did not increase membrane responses to acetylcholine. The CB(1) receptor antagonist SR141716 did not significantly influence EDHF-mediated hyperpolarization except at extremely high concentrations. Smooth muscle cells of third to fourth order branches of the mesenteric artery, which have a more negative resting membrane potential and show smaller responses to acetylcholine, hyperpolarized by about 6 mV to both anandamide and methanandamide, whereas another CB(1) receptor agonist, WIN 55,212-2, had no effect. Mechanical endothelium removal or pre-exposure to SR141716A did not affect anandamide- and methanandamide-induced hyperpolarizations. However, in the presence of capsazepine, a selective vanilloid receptor antagonist, these membrane potential changes were reversed to a small depolarization, whereas EDHF-induced hyperpolarizations were not affected. Pretreating small vessels with capsaicin, causing desensitization of vanilloid receptors and/or depletion of sensory neurotransmitter, completely blocked methanandamide-induced hyperpolarizations. These findings show that anandamide cannot be EDHF. In smooth muscle cells of small arteries, anandamide-induced changes in membrane potential are mediated by vanilloid receptors on capsaicin-sensitive sensory nerves. The different membrane response to the cannabinoids between the main mesenteric artery and its daughter branches might be explained by the different density of perivascular innervation.

Animals↗
PubMed2000

The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin--induced diabetic rats is restored by 5-methyltetrahydrofolate.

AIMS/HYPOTHESIS: Endothelial dysfunction contributes to the development of diabetic vascular complications. A better understanding of the pathophysiology of endothelial dysfunction in diabetes could lead to new approaches to prevent microvascular disease. METHODS: Endothelium-dependent and endothelium-independent vasodilator responses were investigated in the renal microcirculation of streptozotocin-induced diabetic rats. We measured renal blood flow changes with an electromagnetic flow probe. In addition, the responses of the different segments of the renal microcirculation were evaluated with videomicroscopy using the hydronephrotic kidney technique. Because endothelial cells release different relaxing factors (nitric oxide, prostacyclin and an unidentified endothelium-derived hyperpolarizing factor), responses to acetylcholine were measured before and after treatment with the nitric oxide synthase inhibitor L-NG-nitroarginine methylester HCI (L-NAME) and the cyclooxygenase inhibitor indomethacin. We evaluated with the effect of 5-methyltetrahydrofolate, the active form of folate, on the responses. RESULTS: The L-NAME- and indomethacin-resistant vasodilation to intra-renal acetylcholine was significantly reduced in the diabetic compared with control rats, suggesting impaired endothelium-derived hyperpolarizing factor-mediated vasodilation. The responses to the nitric oxide donor (Z)-1-[-2-(aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-i um-1,2-diolate (DETA-NONOate) and to the K+-channel opener pinacidil were similar in diabetics and controls, indicating intact endothelium-independent vasodilator mechanisms. The contribution of endothelium-derived hyperpolarizing factor to vasodilation induced by acetylcholine was greatest in the smallest arterioles. In diabetic rats, the response to acetylcholine was increasingly impared as vessel size decreased. Defective vasodilation in diabetic kidneys was rapidly normalized by 5-methyltetrahydrofolate. CONCLUSION-INTERPRETATION: Endothelium-derived hyperpolarizing factor-mediated vasodilation is impaired in the renal microcirculation of diabetic rats, in particular in the smallest arteries. Treatment with folate restores the impaired endothelial function in diabetes.

Acetylcholine↗
PubMed2000

Endothelial dysfunction in diabetes.

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease. The endothelium controls the tone of the underlying vascular smooth muscle through the production of vasodilator mediators. The endothelium-derived relaxing factors (EDRF) comprise nitric oxide (NO), prostacyclin, and a still elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been demonstrated in various vascular beds of different animal models of diabetes and in humans with type 1 and 2 diabetes. Several mechanisms of endothelial dysfunction have been reported, including impaired signal transduction or substrate availibility, impaired release of EDRF, increased destruction of EDRF, enhanced release of endothelium-derived constricting factors and decreased sensitivity of the vascular smooth muscle to EDRF. The principal mediators of hyperglycaemia-induced endothelial dysfunction may be activation of protein kinase C, increased activity of the polyol pathway, non-enzymatic glycation and oxidative stress. Correction of these pathways, as well as administration of ACE inhibitors and folate, has been shown to improve endothelium-dependent vasodilation in diabetes. Since the mechanisms of endothelial dysfunction appear to differ according to the diabetic model and the vascular bed under study, it is important to select clinically relevant models for future research of endothelial dysfunction.

Animals↗
PubMed2000

EDHF-mediated relaxation in rat gastric small arteries: influence of ouabain/Ba2+ and relation to potassium ions.

In several blood vessels, endothelium-dependent vasorelaxation is in part mediated by an endothelium-derived hyperpolarizing factor (EDHF), the nature of which is as yet unknown. Experiments were performed to investigate whether the recently raised hypothesis that EDHF might be identified as the potassium ion, released by activation of endothelial K(Ca) channels and inducing relaxation by stimulation of Na+/K+-pump and the inward rectifier K+ conductance, might be valid for small rat gastric arteries. EDHF-induced relaxation (assessed as the nitro-L-arginine/indomethacin resistant component of acetylcholine-induced relaxation), but not nitroprus-side-induced relaxation is strongly inhibited in the presence of ouabain (0.5 mM)/Ba2+ (30 microM), ouabain being responsible for the greater part of the inhibition. This inhibition is reversible. Application of increasing concentrations of K+ elicits transient relaxations in some preparations, but in a greater part of the preparations, no or only small relaxations. In membrane potential measurements, it was found that increasing concentrations of extracellular K+ consistently depolarized smooth muscle cells, whereas acetylcholine elicits hyperpolarization. The K(Ca) channel openers NS 1619 and 1-EBIO elicit relaxation effects that are not diminished after removal of the endothelium and are not inhibited by ouabain/Ba2+. It is concluded that EDHF-mediated relaxation is sensitive to inhibition by ouabain/Ba2+, but that the relation of this inhibitory influence to an action of K+ as EDHF is uncertain.

Animals↗
PubMed2000

Pressure-induced myogenic responses in isolated bovine retinal arteries.

PURPOSE: To investigate whether a pressure-induced myogenic vasoconstriction can be demonstrated in isolated bovine retinal arteries and to determine the cellular mechanisms involved. METHODS: Isolated bovine retinal arteries were mounted on a pressure myograph without flow and exposed to stepwise increases in intraluminal pressure. Changes in internal diameter were monitored continuously using an inverted microscope video system. RESULTS: Bovine retinal arteries showed myogenic tone at pressures higher than 10 mm Hg. This pressure-induced contraction was absent in calcium-free Krebs-Ringer bicarbonate solution. Inhibition of L-type voltage-operated calcium channels with nifedipine (1 microM) suppressed the myogenic contraction. After depolarization of the vascular smooth muscle cells with a K+ 120 mM solution, a pressure-induced contraction was still observed, indicating that besides stimulation of voltage-operated calcium channels, depolarization-independent mechanisms contribute to the pressure-induced myogenic vasoconstriction. CONCLUSIONS: Isolated bovine retinal arteries spontaneously contract when exposed to raised intraluminal pressure. This response depends on extracellular calcium and is blocked by nifedipine. In addition, depolarization-independent mechanisms seem to be involved.

Animals↗
PubMed2000

A retinal-derived relaxing factor mediates the hypoxic vasodilation of retinal arteries.

PURPOSE: To investigate the mechanisms involved in hypoxic vasodilation using an in vitro setup. METHODS: Retinal arteries with and without retinal tissue were mounted on a wire myograph. The segments were contracted with prostaglandin (PG)F(2alpha) (30 microM) or 120 mM K(+). Hypoxia was induced by replacement of O(2) by N(2) in the gas used to bubble the Krebs-Ringer bicarbonate organ bath solution. RESULTS: Hypoxia induced complete relaxation of preparations with adherent retinal tissue contracted with PGF(2alpha). Preparations without retinal tissue were not affected by the change in oxygenation. When the retinal arteries were contracted with 120 mM K(+), hypoxia no longer induced relaxation of the preparation with adherent retinal tissue. The presence of an NO-synthase inhibitor (L-NA, 0.1 mM), a cyclooxygenase inhibitor (indomethacin, 50 microM), or an adenosine receptor antagonist (8-sulfophenyltheophylline, 1 mM) did not affect hypoxic vasodilation. Excitatory amino acids and lactate had no or only a limited effect on the PGF(2alpha)-induced contraction and are therefore unlikely mediators of hypoxic vasodilation. HCl (10 mM) reduced the pH to 6.1 +/- 0.08 (n = 4) and induced a pronounced but transient relaxation of the retinal artery contracted with PGF(2alpha) or 120 mM K(+), whereas hypoxia induced relaxation of the retinal artery contracted with PGF(2alpha) only in the presence of adherent retinal tissue. CONCLUSIONS: Adherent retinal tissue mediates the hypoxic vasodilatation of bovine retinal arteries in vitro. Neither NO, prostanoids, adenosine, excitatory amino acids lactate or changes in pH seem to be involved in this hypoxic response.

Animals↗
PubMed1999

Protective effect of cromakalim and diazoxide, and proulcerogenic effect of glibenclamide on indomethacin-induced gastric injury.

We investigated the influences of the K+ channel opening drugs cromakalim and diazoxide and their blocker, glibenclamide, in indomethacin-induced gastric injury in rats. Cromakalim (0.1 and 0.3 mg/kg) and diazoxide (10 and 30 mg/kg) produced dose-dependent gastroprotection at doses that were also effective on the cardiovascular system. Glibenclamide reversed their gastroprotective effects and aggravated indomethacin-induced gastric damage by its own. Cromakalim (10(-9)-10(-5) M) and diazoxide (10(-9)-10(-4) M) relaxed noradrenaline pre-contracted gastric arteries (94.59+/-1.58% and 93.86+/-2.99%, respectively). Their relaxant effects were inhibited by glibenclamide (10(-5) M) but not by indomethacin (10(-5) M) and LG-nitro-L-arginine (10(-4) M). Cromakalim (0.1 and 0.3 mg/kg) did not change gastric mucosal blood flow but increased the gastric mucosal vascular conductance in anaesthetized rats as measured by the hydrogen gas clearance technique. Indomethacin increased myeloperoxidase activity in the gastric mucosa, an effect which was reversed by cromakalim and diazoxide. Glibenclamide abolished their effects on myeloperoxidase activity and, alone, increased this parameter. Additionally, indomethacin caused infiltration of neutrophils which was reduced by cromakalim and diazoxide in a glibenclamide sensitive manner. The effects of cromakalim and diazoxide on mucosal myeloperoxidase activity, neutrophil infiltration and gastric injury correlated with each other. The effects of diazoxide (30 mg/kg) and glibenclamide (10 mg/kg) on blood glucose level were not correlated with their effects on gastric injury. Taken together, K+ channel opening drugs show misoprostol-like protective effects in indomethacin-induced gastric injury which seems to be related to modulation of neutrophil function.

Animals↗
PubMed1999

Urinary excretion of tubular proteins and the technetium-99m dimercaptosuccinic acid (DMSA) absolute renal uptake in partial ureteral obstruction in rats: a functional evaluation of hydronephrotic kidneys.

The aim of this longitudinal study was to evaluate tubular proteinuria in rats with unilateral (UPO) and bilateral (BPO) partial ureteral obstruction with the dimercaptosuccinic acid (DMSA) scan as the gold standard for measuring renal tubular damage. We studied 70 female Wistar rats: 28 animals with UPO, 28 animals with BPO, 7 sham-operated animals, and 7 controls. All animals with obstructed ureters showed renal dilatation on the diethylenetriaminepentaacetic acid DTPA images 1 and 5 weeks postoperatively. One week following UPO and BPO, tubular proteinuria and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity increased (P < 0.01) and the absolute DMSA uptake decreased (P < 0.01). Persistently (week 6) high tubular proteinuria was found in 29% of the animals and was related to severe damage on the DMSA scan (P < 0.01) and to albuminuria (P < 0.05). Renal tubular damage was demonstrated by measuring renal enzymes, tubular proteins, and DMSA uptake after UPO and BPO. Persistent elevated tubular proteinuria was related to severely damaged kidneys.

Acetylglucosaminidase↗
PubMed1999

Barium decreases endothelium-dependent smooth muscle responses to transient but not to more prolonged acetylcholine applications.

The influence of inhibiting the inward rectifier and Na/K pump on endothelium-dependent hyperpolarizations in smooth muscle cells of the mesenteric artery was investigated. Membrane potential was measured with microelectrodes, and the influence of low concentrations of Ba2+ (30 microM) and of high concentrations of ouabain (0.5 mM) on smooth muscle hyperpolarization elicited by prolonged or by transient exposure to acetylcholine (ACh, 3x10(-7) M) was assessed in the continuous presence of NG-nitro-L-arginine (100 microM) and indomethacin (50 microM). Pre-exposure to Ba2+ did not inhibit the magnitude of smooth muscle cell hyperpolarization induced by ACh superfusion, but significantly slowed its onset and time course. The membrane potential response to transient ACh applications, however, was impaired. After combined Ba2+ and ouabain pre-exposure, peak hyperpolarizations to ACh superfusion were somewhat decreased but not abolished. In addition, 4-5 mM increases of the extracellular K+ concentration consistently depolarized smooth muscle cells. These findings argue against the idea that smooth muscle inward rectifier K+ channels and Na/K pumping play a role in the ACh-induced endothelium-dependent hyperpolarization of this preparation. Moreover, the slowing of smooth muscle membrane hyperpolarization by Ba2+ is discussed in terms of the influence of this ion on the release of hyperpolarizing factor.

Acetylcholine↗
PubMed1999

Beneficial effect of serotonin 5-HT2-receptor antagonism on renal blood flow autoregulation in cyclosporin-treated rats.

Renal blood flow (RBF) autoregulation reappears in postischemic rat kidneys during serotonin (5-HT2) antagonism. The aim of the present study was to analyze whether 5-HT2 antagonism can ameliorate impaired RBF autoregulation in rats treated with 20 mg/kg per d cyclosporin A during 10 d. Autoregulation of RBF was assessed during stepwise lowering of renal perfusion pressure from 110 to 70 mmHg by gradual compression of the aorta. Autoregulation was lost in the cyclosporin A-treated rats. During administration of the 5-HT2 antagonist ritanserin (0.6 mg/kg intravenous bolus, followed by 1.2 mg/kg per h intravenous infusion during 1 h), autoregulation acutely reappeared. Intrarenal bolus injections of a selective 5-HT2-agonist, 2,5 dimethoxy-4-iodoamphetamine hydrochloride, elicited a significantly stronger renal vasocontraction in cyclosporin A-treated rats than in control rats. This finding was also observed with serotonin after nitric oxide-synthase blockade. These results (1) show the importance of 5-HT2-receptor-mediated vasoconstriction in the suppression of vasodilatory autoregulation of RBF in experimental cyclosporin A-induced renal dysfunction and (2) demonstrate that the complete loss of RBF autoregulation is not due to damage of the vascular smooth muscle cells.

Animals↗
PubMed1999

Influence of some phospholipase A2 and cytochrome P450 inhibitors on rat arterial smooth muscle K+ currents.

The hyperpolarizing factor that is liberated by vascular endothelial cells in response to various agonists, and known to induce relaxation by opening of smooth muscle K+ channels, has been suggested to be a product of cytochrome P450 dependent arachidonic acid metabolism. In this study, the direct influence of two phospholipase A2 inhibitors and of five structurally and mechanistically different cytochrome P450 inhibitors on K+ currents in freshly isolated vascular smooth muscle cells from the rat aorta was investigated. On stepping the cell membrane potential from -70 mV to a series of depolarized test potentials, a noisy outward current developed at test potentials > +10 mV, which showed no appreciable inactivation during the voltage pulse. It was largely abolished by 3 mM external tetraethylammonium chloride (TEA), suggesting that it predominantly consisted of current through large-conductance Ca(2+)-activated K+ channels. The phospholipase A2 inhibitor quinacrine considerably inhibited this TEA-sensitive current, while 4-bromophenacylbromide exerted no effect. The cytochrome P450 inhibitors proadifen and miconazole reversibly decreased the amplitude of I(K), while clotrimazole and 1-aminobenzotriazole had no effect. Conversely, 17-octadecynoic acid increased whole-cell I(K). These results show that some phospholipase A2 and cytochrome P450 inhibitors may interfere with K+ channel activation in the rat arterial smooth muscle cell. The relevance of these findings to studies on the involvement of cytochrome P450 dependent metabolism in the generation of the endothelium-derived hyperpolarizing factor in intact arteries is discussed.

Animals↗
PubMed1998

Retinal arterial tone is controlled by a retinal-derived relaxing factor.

The present study provides evidence that retinal tissue may profoundly influence the retinal arterial smooth muscle cell tone by releasing an unknown retinal relaxing factor. Isolated bovine retinal arteries with and without adhering retinal tissue were mounted in a wire myograph for isometric tension recordings. The maximal contraction induced by prostaglandin F2alpha was 0.95+/-0.7 mN (n=6) in the presence and 5.15+/-0.76 mN (n=6) in the absence of adhering retinal tissue. The contractions induced by U-46619, serotonin, and endothelin-1 were similarly blocked in the presence of retinal tissue. The K+ 120 mmol/L-induced contraction was not significantly affected (2.8+/-0.7 mN, n=6, in the presence and 3. 6+/-0.7 mN, n=6, in the absence of retinal tissue). Placing a piece of bovine retinal tissue in the proximity of a contracted (ie, with prostaglandin F2alpha) retinal artery induced a complete relaxation of the retinal vessel, suggesting the involvement of a diffusible chemical vasorelaxant. Also porcine, canine, and ovine retinal tissue completely relaxed the contracted (with prostaglandin F2alpha) bovine retinal artery. Other smooth muscle preparations, including rat mesenteric and renal arteries and rat main bronchi, also relaxed with the application of a piece of bovine retinal tissue. Incubation of bovine retinas in a Krebs-Ringer bicarbonate solution yielded a solution that relaxed isolated precontracted bovine retinal arteries, confirming the involvement of a diffusible chemical messenger. Hexane extraction, heating the solution to 70 degrees C, or treatment with trypsin did not alter the relaxing properties of the incubation solution. The characteristics of the retinal relaxing factor do not correspond with those of nitric oxide, prostanoids, adenosine, acetylcholine, or any other of the known vasoactive neurotransmitters released from the retina. Our results suggest that retinal arterial tone is controlled by a diffusible, hydrophilic, and heat-stable relaxing factor that does not correspond with a known vasoactive molecule formed within the retina.

Animals↗
PubMed1998

Mechanisms involved in the vasorelaxing influence of histamine on isolated human subcutaneous resistance arteries.

The effects of histamine were analysed on human subcutaneous small arteries. No effect was seen on non-precontracted preparations. After precontraction (norepinephrine 1 microM and K+ 30 mM) histamine potently relaxed the arteries (EC50 = 0.3 microM; max. effect = 95% relaxation). The histamine H1 receptor antagonist, pyrilamine (10 microM), had only a small, non-significant inhibitory influence on histamine-induced relaxation while the histamine H2 receptor antagonist, cimetidine (0.1 mM), had a significant inhibitory influence. Relaxation was completely blocked in the presence of both antagonists. Both 2-pyridylethylamine (histamine H1 receptor agonist) and dimaprit (histamine H2 receptor agonist) elicited relaxation. Removal of endothelium reduced the relaxation effects of histamine and 2-pyridylethylamine, but not of dimaprit. Inhibition of nitric oxide synthesis by nitro-L-arginine significantly inhibited histamine-induced relaxation and even more clearly the cimetidine-resistant component. We conclude that histamine potently relaxes human subcutaneous arterioles, and that most probably both muscular histamine H2 receptors and endothelial histamine H1 receptors, thus activating nitric oxide release, contribute to the relaxation.

Adipose Tissue↗
PubMed1998

Elevated tubular proteinuria, albuminuria and decreased urinary N-acetyl-beta-D-glucosaminidase activity following unilateral total ureteral obstruction in rats.

UNLABELLED: Urinary tubular proteinuria and N-acetyl-beta-D-glucosaminidase (NAG) activity has not yet been studied after unilateral total ureteral obstruction (UTO). The aim of the study was (1) to evaluate in a longitudinal study (7 weeks) the behaviour and the potential clinical value of tubular proteinuria and urinary NAG activity after UTO; (2) to study the physiopathology of the non-obstructed contralateral kidney by using these two different markers of tubular damage. METHODS: in 28 female, adult Wistar rats (UTO: n = 16, sham: n = 12), tubular proteinuria and urinary NAG activity were measured before and 1 and 5 weeks after surgery. RESULTS: a significant (P < 0.01) increase in tubular proteinuria/creatinine ratio and urinary creatinine and a decrease in urinary NAG activity was found 1 week after UTO. All parameters normalized after 6 weeks. Albuminuria increased progressively (P < 0.01) during the study. CONCLUSION: tubular proteinuria increases during the first week following UTO in rats. The initial increase of low molecular weight proteins following UTO is not due to tubular damage as no parallel increase of urinary NAG was found. We suggest an initial tubular overperfusion with primary urine, due to an increased single nephron glomerular filtration and overruling the reabsorption capacity of the proximal tubules.

Acetylglucosaminidase↗