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Biomedical subjects

C de Wit

Publications and source records attributed to C de Wit.

10 recordsLinked to original sources
PubMed1996

Interaction of nitric oxide with myogenic and adrenergic vasoconstrictor processes in the control of microcirculatory blood flow.

Since the early observations of Carl Ludwig that the sympathetic nervous system exerts a tonic influence on resistance vessels, many additional factors have been identified which control vascular tone. The active modulator role of endothelium-derived nitric oxide (NO) in this process has emerged only in the last decade. The interaction of the local vasodilator, NO, with systemic alpha-adrenergic control of vascular tone as well as with pressure-induced myogenic vasoconstriction is briefly reviewed in the present paper. Cellular mechanisms of this interaction are discussed. In vitro and in vivo experiments indicate that the continuous basal release of NO potently attenuates alpha-adrenergic and myogenic tone in resistance vessels by several independent mechanisms and that endothelial impairment results in abnormal vasoconstriction.

Animals↗
PubMed1994

Synergistic action of vasodilators that increase cGMP and cAMP in the hamster cremaster microcirculation.

OBJECTIVE: Compounds such as endothelium derived nitric oxide (NO) and prostacyclin (prostaglandin I2) which increase cGMP and cAMP inhibit platelet activation in a synergistic manner. The aim of this study was to examine whether these compounds also interact synergistically in the control of smooth muscle tone. METHODS: Vascular diameters in the cremaster of 49 anaesthetised hamsters (465 arterioles) were studied during superfusion with compounds raising cAMP (isoprenaline and prostacyclin) and cGMP (sodium nitroprusside) alone or in combination. RESULTS: (1) The isoprenaline induced maximum dilator response was significantly attenuated, from 86.1(SEM 0.7)% to 37.1(0.2)%, after inhibition of NO-synthase with NG-nitro-L-arginine (L-NNA, 30 microM). Superfusion with sodium nitroprusside (30 nM, dilatation alone: 6.7%), which was used to substitute for endothelium derived NO, restored the attenuated isoprenaline response. The combined effects of isoprenaline and sodium nitroprusside were supra-additive. Virtually identical results were obtained when prostacyclin, another cAMP raising compound, was used instead of isoprenaline. The K+ channel opener cromakalim (100 nM) which acts cGMP independently was without effect on the prostacyclin induced dilator response. (2) The sodium nitroprusside induced maximum dilator response was attenuated from 80.9(0.25)% to 70.1(0.4)%, after indomethacin (3 microM) and restored by simultaneous application of prostacyclin (1 nM, dilatation alone: 1.4%) but not of cromakalim. Again, the combined effects were supra-additive, suggesting a synergistic action of these compounds. (3) Although indomethacin or L-NNA alone decreased the resting diameter by approximately 9.5%, the simultaneous application of both inhibitors failed to decrease the resting diameter further (10.0%, p = 0.97). CONCLUSIONS: Vasodilators increasing cGMP and cAMP act synergistically in vivo. Continuous release of NO and prostaglandins by the endothelium may therefore not only modulate the efficacy of such cyclic nucleotide increasing vasodilators but also interact synergistically in controlling basal vascular tone.

Abdomen↗
PubMed1993

A developmental decrease in NMDA-mediated spontaneous firing in cultured rat cerebral cortex.

In primary cultures of fetal rat cerebral cortex chronic manipulation of the level and/or pattern of bioelectric activity leads to plastic changes in bioelectric activity, opposite to those seen during the manipulation. This suggests the presence of adaptive mechanisms which regulate functional development in the neuronal network. Since NMDA receptors play an important role in early postnatal bioelectric activity and have been implicated in activity-dependent plasticity in vivo, the involvement of NMDA and non-NMDA receptors in spontaneously occurring bioelectric activity was investigated in cultured rat cerebral cortex by assaying the effects of NMDA and non-NMDA antagonists on neuronal firing. In addition, the physiological consequences of chronic suppression of bioelectric activity were investigated following development in the presence of tetrodotoxin. NMDA receptors appeared at all ages to be more crucial for spontaneous bioelectric activity than non-NMDA receptors, although their relative importance decreased during the first 3 weeks. Whereas the NMDA antagonist APV strongly reduced burst firing, the non-NMDA antagonist DNQX tended to increase burst firing slightly. Following chronic suppression of bioelectric activity, non-variable burst firing was increased, thus replicating previous findings in cerebral cortex culture grown under different conditions. The prominence of NMDA receptor activation in spontaneous bioelectric activity in early cultures suggests a role for these receptors in activity-dependent functional plasticity, as found in vivo.

2-Amino-5-phosphonovalerate↗
PubMed1993

Endothelium-derived nitric oxide in the control of tissue perfusion and oxygen supply: physiological and pathophysiological implications.

Since the development of specific NO-synthase inhibitors it has become possible to study the role of NO in the control of local blood flow and tissue oxygenation. Inhibition of NO-synthase induces hypertension and abnormal vasoconstriction, as well as tissue hypoxia and impaired adaptation of blood flow to increased tissue oxygen demands. These functional alterations are similar to those observed in a number of cardiovascular diseases. The present evidence that impaired endothelial function is a pathogenetic factor in the development of cardiovascular diseases is briefly reviewed.

Animals↗
PubMed1991

Demonstration of a phospholipase A2 inhibitor in human plasma and in plasma from the European hedgehog (Erinaceus europaeus).

1. Endogenous phospholipase A2 (PLA2) inhibitors in human plasma and in plasma from the hedgehog (Erinaceus europaeus) were demonstrated. 2. The PLA2 activity increased 45-fold in human plasma when a PLA2 binding factor was removed. Furthermore, two peaks of PLA2 inhibitory activity were found after DEAE-chromatography. 3. High levels of PLA2 inhibitory activity was found in plasma from the European hedgehog, E. europaeus. 4. The molecular weight was estimated to 140,000. 5. On DEAE-chromatography two peaks were found which were chromatographically similar to the PLA2 inhibitors in human plasma.

Adult↗
PubMed1991

Experimental studies on the nephrotoxicity of amphotericin B in rats.

The renal effects of amphotericin B alone and in combination with cyclosporin A, tobramycin, fosfomycin, D-glucaro-1,5-lactam and verapamil were studied in rats. The parameters for nephrotoxicity were urinary loss of tubular cells and malate dehydrogenase, as well as creatinine clearance. Repeated intraperitoneal injections of amphotericin B led to an increase of urinary tubular cell elimination and malate-dehydrogenase. After co-administration of amphotericin B and cyclosporin A, the urinary loss of tubular cells increased and creatinine clearance was reduced. A combination of amphotericin B and tobramycin reduced tubular cell elimination but the creatinine clearance improved. When verapamil was combined with amphotericin B, endogenous creatinine clearance increased, though the loss of tubular cells was elevated. Furthermore, fosfomycin reduced the loss of tubular cells and improved renal functional parameters in combination with amphotericin B. In addition, D-glucaro-1,5-lactam was found to reduce the urinary loss of tubular cells induced by amphotericin B.

Amphotericin B↗
PubMed1991

Swedish dioxin survey: evaluation of the H-4-II E bioassay for screening environmental samples for dioxin-like enzyme induction.

The H-4-II E enzyme induction bioassay was used for testing both pure reference substances and extracts of wildlife samples. Polychlorinated naphthalenes were found to be as active as enzyme inducers as certain coplanar polychlorinated biphenyls (PCBs). Also a mixture of polybrominated diphenyl ethers (Bromkal 70-5DE) was shown to induce enzyme activity. In extracts of herring, containing polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), bioassay and chemically derived TCDD-equivalents (TEQs) were nearly identical. When extracts containing other types of dioxin-like compounds as well were tested, the bioassay TEQs for most of them agreed well with chemical TEQs calculated for PCDDs, PCDFs and non-ortho PCBs. However, for ringed seal and whitefish, TEQs obtained from the bioassay were higher than those from the chemical analysis. Our results indicate that this bioassay is an excellent complement to chemical residue analysis and a useful tool in understanding the complex interactions of halogenated hydrocarbons. For risk assessment, such results should, however, be used most carefully as they are measured in vitro.

Animals↗
PubMed1990

Experimental studies on nephrotoxicity and pharmacokinetics of LY 146032 (daptomycin) in rats.

The nephrotoxicity and pharmacokinetics of LY 146032 (daptomycin) were studied in an experimental rat model. Nephrotoxicity was assessed by measuring urinary loss of tubular cells and malate dehydrogenase. LY 146032 (10-250 mg/kg daily iv) led to a dose-dependent and reversible increase of cell elimination. The tubulo-toxic threshold dose is stated to be 10 mg/kg daily. Nephrotoxicity induced by LY 146032 can be reduced by coadministration of fosfomycin or D-glucaro-1.5-lactam, and enhanced by combination with tobramycin. LY 146032 accumulated in renal tissue during repeated administration. Electron microscopy revealed histopathological changes in the kidneys. Therefore the nephrotoxic potential of LY 146032 should be taken into consideration in clinical trials.

Animals↗
PubMedDate not supplied

Mediator role of prostaglandins in acetylcholine-induced vasodilation and control of resting vascular diameter in the hamster cremaster microcirculation in vivo.

Acetylcholine (ACh) is widely used as a standard test substance for nitric oxide (NO)-mediated vasodilation. However, it also augments the release of prostaglandins, a group of other endothelium-derived smooth muscle relaxants. Using intravital microscopy in the cremaster muscle of anesthetized hamsters, we studied the relative roles of NO and prostaglandins in mediating ACh-induced dilation and in the control of basal vessel tone (253 arterioles in 31 experiments) N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of NO synthase, significantly reduced ACh-induced vasodilation (by 42-73%), irrespective of whether it was applied intravenously (30 mg/kg) or topically (30 microM). Additional indomethacin (3 microM, topical) nearly abolished the dilator response. In contrast, the vascular responses to the endothelium-independent dilator sodium nitroprusside were not affected. The resting diameters (range: 6-114 microns) were significantly (p < 0.05) reduced after L-NNA or indomethacin by 10.2 and 16.6% of control diameter, respectively. The constriction induced by L-NNA was stronger in larger (> 50 microns) than in smaller (< 50 microns) vessels, whereas indomethacin was equipotent in both groups. Thus, in addition to NO, dilating prostaglandins are important mediators of the ACh-induced dilation and contribute to the control of resting arteriolar diameter in the hamster cremaster microcirculation in vivo.

Abdominal Muscles↗