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Biomedical subjects

C Wanner

Publications and source records attributed to C Wanner.

At least 91 records · Page 5Linked to original sources
PubMed1996

Cholesterol metabolism in glomerular cells: effect of lipoproteins from nephrotic patients.

Although hyperlipidemia is a well recognized complication of the nephrotic syndrome, the precise metabolism of human lipoproteins by human glomerular cells and the effects of abnormalities in lipid and protein composition on this process have not been defined. This study examined the effects of apoB-100 containing low-density-lipoprotein (LDL) and apo B,E, containing intermediate-density lipoprotein (IDL), isolated from patients with the nephrotic syndrome (n = 6), on intracellular sterol synthesis and cholesterol esterification by human glomerular epithelial and mesangial cells. For comparison studies, human skin fibroblasts and Hep G2 cells were used. In the patients, serum LDL cholesterol level was increased threefold and IDL tenfold as compared to healthy subjects. LDL of nephrotic patients showed no differences in lipid/protein composition as compared to control LDL but IDL contained 58% more cholesterol than IDL from healthy controls. Therefore, nephrotic and control LDL showed identical inhibition of intracellular sterol synthesis and similar cholesteryl ester formation in all the four cell types. In contrast, cholesterol-rich IDL of nephrotic patients suppressed intracellular sterol synthesis more effectively than control IDL. The cholesterol esterification rate of IDL from patients was enhanced three fold on average as compared to control IDL. The various cell types differed in their rate of LDL esterification. The data indicate that the enhanced inhibition of intracellular sterol synthesis and cholesterol esterification by apo E-containing cholesterol-ester-rich IDL, which accumulate in nephrotic patients, may render these lipoproteins possible candidates for glomerular lipid deposition and progressive renal injury.

Adult↗
PubMed1996

Endotoxin-induced acute renal failure in the rat: effects of urodilatin and diltiazem on renal function.

Acute renal failure (ARF) due to endotoxins is a common problem in clinical medicine. Endotoxins are released from the outer membrane of the gram-negative bacterial envelope and are composed of lipopolysaccharides (LPS). Although systemic hypotension often is present, LPS-induced ARF is characterized by marked intrarenal vasoconstriction. Both calcium channel blockers and natriuretic peptides are able to antagonize vasoconstricting signals and have been reported to exert beneficial effects in toxic and ischemic ARF: We investigated the effects of diltiazem (Dil, 300 micrograms/kg) or urodilatin (Uro, 40 micrograms/kg) or a combination of both (same doses) on renal function in early LPS-induced ARF: One hour after induction of ARF by i.v. injection of LPS glomerular filtration rate (GFR, clearance of fluorescence-marked inulin) was distinctly reduced to about 54% of basal values. In the following infusion period (60 min) a significant increase of GFR was observed with diltiazem (1.54 +/- 0.11 ml/min), urodilatin (1.60 +/- 0.10 ml/min) and the combination of both drugs (1.66 +/- 0.04 ml/min) compared to controls (1.17 +/- 0.08 ml/min). Combined administration did not cause additive effects. Also 60 and 120 minutes after stopping of drug infusion elevated GFR could be maintained in all experimental groups. Due to their vasorelaxing activity both Uro and Dil induced a decrease of mean arterial blood pressure in comparison with controls and revealed remarkable diuretic and natriuretic activity. In conclusion our results underline that marked intrarenal vasoconstriction in LPS-induced ARF can be antagonized by the well known relaxing potency of Uro and Dil towards vascular smooth muscle and mesangial cells. Both Uro and Dil were capable of improving suppressed renal function in the early phase of LPS-induced ARF in the rat as long as severe systemic hypotension is absent.

Acute Kidney Injury↗
PubMed1996

Hemorheology, plasma protein composition and von Willebrand factor in type I diabetic nephropathy.

Patients with IDDM, especially those with albuminuria are at high risk for macrovascular and microvascular complications. Besides the major classic risk factors altered hemorheology may also play a role. Plasma viscosity, erythrocyte aggregation and erythrocyte deformability are the major determinants of blood flow in the microcirculation. Therefore, these hemorheological parameters and plasma protein composition were evaluated in 58 IDDM-patients with none (N0), incipient (N1: albuminuria 30-300 mg/day) and overt clinical nephropathy (N2: albuminuria > 300 mg/day). As an estimate of endothelial injury plasma levels of von Willebrand Factor (vWF) were investigated. Patients with incipient and clinical nephropathy exhibited increasing blood levels of fibrinogen (N0 = 2.47 +/- 0.09, N1 = 2.71 +/- 0.15, N2 = 3.49 +/- 0.24 g/l, p < 0.001), alpha 2-macroglobulin (N0 = 257 +/- 11, N1 = 251 +/- 21, N2 = 382 +/- 43 mg/100 ml, p < 0.01) and haptoglobin (N0 = 174 +/- 16, N1 = 216 +/- 39, N2 = 278 +/- 36 mg/100 ml, p < 0.05), whereas serum albumin concentration decreased (N0 = 5.1 +/- 0.1, N1 = 4.7 +/- 0.1, N2 = 4.1 +/- 0.2 g/100 ml, p < 0.001). In the same patients erythrocyte aggregation (N0 = 10.0 +/- 0.4, N1 = 12.1 +/- 0.5, N2 = 12.9 +/- 0.6, p < 0.001), plasma viscosity (N0 = 1.34 +/- 0.01, N1 = 1.38 +/- 0.02, N2 = 1.40 +/- 0.02 mPas, p < 0.05) and erythrocyte rigidity (N0 = 0.05 +/- 0.01, N1 = 0.15 +/- 0.05, N2 = 0.09 +/- 0.02, p < 0.05) were increased, predominantly in those with overt clinical nephropathy. Erythrocyte aggregation was positively correlated with plasma concentrations of fibrinogen (r = 0.65, p < 0.001) and alpha 2-macroglobulin (r = 0.35, p < 0.05), but negatively with plasma albumin concentration (r = -0.49, p < 0.001). Plasma viscosity was positively correlated with plasma concentrations of fibrinogen (r = 0.46, p < 0.001) and haptoglobin (r = 0.46, p < 0.001). Von Willebrand Factor levels were higher in patients with overt clinical nephropathy (N0 = 126 +/- 8, N1 = 136 +/- 12, N2 = 163 +/- 14%, p < 0.09, PN0-N2 < 0.05). A significant correlation between vWF and the rheological determinants could not be detected. These data demonstrate that blood rheology is profoundly altered in patients with IDDM and nephropathy. Elevated levels of vWF may indicate endothelial damage, and changes in plasma viscosity as well as erythrocyte aggregability seem to be the result of altered plasma protein composition due to proteinuria. These abnormalities in hemorheology may be an aggravating factor promoting microvascular and macrovascular damage in patients with type I diabetes mellitus and nephropathy.

Adult↗
PubMed1996

Potential role of lipids in the progression of diabetic nephropathy.

Dyslipoproteinemia in non-insulin-dependent diabetes mellitus (NIDDM) is an important risk factor in the development of atherosclerosis and glomerulosclerosis. The lipid profile of NIDDM patients is characterized by elevated serum triglycerides and VLDL levels and reduced HDL cholesterol levels. Serum LDL levels may be elevated as well in some patients with NIDDM, but several alterations in the biochemical and physical properties of LDL particles are more characteristic resulting in reduced receptor specific uptake of these lipoproteins. Non-enzymatic glycosylation of LDL and augmented oxidation is common in diabetic patients making lipoproteins susceptible for uptake by the macrophage scavenger receptors and thus leading to foam cell formation and further glomerular damage. A reduction in the progression of diabetic nephropathy by lowering proteinuria and thereby serum cholesterol during treatment with ACE-inhibitors demonstrates the importance of such a therapy. The multiple factors involved in the pathogenesis of diabetic nephropathy are difficult to evaluate in regard to their individual contribution. Nevertheless antiproteinuric and lipid lowering therapy can be expected to reduce vascular damage and the progression of diabetic nephropathy.

Animals↗
PubMed1996

Is the determination of LDL cholesterol according to Friedewald accurate in CAPD and HD patients?

Lipid abnormalities are a major cause of accelerated atherosclerosis in patients with end-stage renal disease. In many clinical laboratories, the concentration of low density lipoproteins (LDL), the most atherogenic lipoprotein fraction, is estimated by calculating LDL cholesterol according to Friedewald. Hypertriglyceridemia, a common finding in uremic patients, is a main limitation to the use of the Friedewald formula, and the estimation of LDL cholesterol may, therefore, not be reliable in these patients. As accurate quantitation of LDL cholesterol is needed to decide on the initiation of lipid lowering therapy, we have evaluated the accuracy of the Friedewald formula in 171 patients on continuous ambulatory peritoneal dialysis (CAPD), 136 hemodialysis (HD) patients and 887 clinically healthy individuals by comparing it with a combined ultracentrifugation and precipitation 'reference' method. When we excluded sera with total triglycerides above 400 mg/dl [4.56 mmol/l], the Friedewald formula correlated excellently with the reference method; non-parametric correlation coefficients were 0.976, 0.971, and 0.956 in clinically healthy individuals, CAPD and HD patients, respectively. In the control individuals, the Friedewald formula produced slightly lower concentrations of LDL cholesterol than the reference method (means: 142 +/- 40 mg/dl vs 150 +/- 39 mg/dl or 3.68 + 1.04 mmol/l vs. to 3.89 + 1.01 mmol/l, respectively). This was also true in HD patients (means: 145 +/- 51 vs. 146 +/- 49 mg/dl or 3.76 +/- 1.32 vs. 3.78 +/- 1.27 mmol/l, respectively), but not in CAPD patients (means: 165 +/- 50 vs. 162 +/- 47 mg/dl or 4.27 +/- 1.30 vs. 4.20 +/- 1.22 mmol/l). Our data show that, unlike in other forms of secondary dyslipoproteinemia, the Friedewald formula is sufficiently reliable in patients with end-stage renal disease. Much the same, however, as in control individuals, other methods to quantify LDL cholesterol like ultracentrifugation or lipoprotein electrophoresis are recommended when serum triglycerides exceed 400 mg/dl [4.56 mmol/l].

Case-Control Studies↗
PubMed1995

Impairment of endothelium-dependent dilation in rabbit renal arteries by oxidized lipoprotein(a). Role of oxygen-derived radicals.

BACKGROUND: Hyperlipoproteinemia is associated with impairment of nitric oxide (NO)-mediated, endothelium-dependent dilation in renal arteries. In the present study, we assessed and compared the effects of human lipoprotein(a) and LDL on endothelium-dependent and -independent dilation in vitro. METHODS AND RESULTS: Dilator responses were detected in isolated, saline-perfused, preconstricted arterial segments by a photoelectric device. Acetylcholine-induced, endothelium-dependent dilator responses of rabbit renal arteries were not significantly attenuated after 150 minutes of incubation with native lipoprotein(a) (30 and 100 micrograms/mL). However, exposure to in vitro oxidized lipoprotein(a) (150 minutes, 30 and 100 micrograms/mL) suppressed acetylcholine-induced dilator responses in a dose-dependent manner. At similar concentrations, native and oxidized LDL had no effect. Endothelium-independent dilations induced by the NO-donor sodium nitroprusside were also impaired by oxidized lipoprotein(a), whereas forskolin-induced dilator responses were unaffected, indicating that smooth muscle dilator capacity was not impaired. Attenuation of dilator responses by oxidized lipoprotein(a) was potentiated in the presence of superoxide dismutase (SOD). The SOD effect was completely blunted by coincubation with catalase (100 U/mL) or deferoxamine. In the absence of SOD, catalase or deferoxamine had no effect on dilator responses. Using a chemiluminescence assay, we could detect increased O2- production by arteries pretreated with oxidized lipoprotein(a), which suggested that enhanced NO inactivation by O2- could be the underlying mechanism for impairment of endothelium-dependent dilations. CONCLUSIONS: These data indicate that oxidized lipoprotein(a) impairs endothelium-dependent dilation and is more potent than oxidized LDL in this effect. The mechanism of the impairment may involve formation of O2- and inactivation of NO.

Animals↗
PubMed1995

Oxidized LDL and lipoprotein(a) stimulate renin release of juxtaglomerular cells.

Atherogenic lipoproteins accumulate in the arterial wall and may potentially stimulate neighboring cells. In the glomerulus the vascular pole resembles afferent arteries in close vicinity to the juxtaglomerular apparatus. We examined the effects of native and oxidized LDL and lipoprotein(a) [Lp(a)] on renin release of juxtaglomerular cells (JG cells) prepared in primary culture from mouse kidneys. Renin activity of JG cells was measured in culture supernatants and cells between the 20th and 40th hour of culturing. Spontaneous renin release into the cell supernatant was 26 +/- 1% of total activity. Control stimulation of JG cells by melittin or forskolin dose-dependently increased renin release up to 90 +/- 2%. Incubation of JG cells with native LDL (50 and 300 micrograms/ml) or native Lp(a) (30 micrograms/ml) did not alter renin release. Oxidized LDL increased renin release to 34 +/- 1% and 43 +/- 1% at 50 and 300 micrograms/ml, while oxidized Lp(a) stimulated renin release to 33 +/- 1%, 42 +/- 1%, and 71 +/- 2% at 1, 10, and 30 micrograms/ml, respectively. Coincubation with superoxide dismutase and catalase, enzymes removing O2- and H2O2, completely eliminated oxidized LDL and Lp(a)-stimulated renin release. In the absence of lipoproteins, renin release was significantly stimulated by activation of O2- formation by the xanthine/xanthine oxidase reaction. These data indicate that oxidized LDL and Lp(a) stimulate renin release in JG cells by a mechanism involving oxygen-derived radicals. Thus, oxidatively modified atherogenic lipoproteins may contribute to renin-dependent hypertension in renoparenchymatous kidney disease.

Animals↗
PubMed1995

Clinical course of patients with antineutrophil cytoplasm antibody positive vasculitis after kidney transplantation.

Four patients with antineutrophil cytoplasm antibody (ANCA)-positive vasculitis were followed over a period from 27 to 54 months after successful kidney transplantation under immunosuppressive treatment with ciclosporine. ANCA titer prior to transplantation was markedly elevated and decreased in 1 of 4 patients under therapy with ciclosporine. Despite adequate ciclosporine blood trough levels, a relapse occurred in 2 patients 18 and 24 months after transplantation but therapy with cyclophosphamide induced remission and no patient lost his graft due to relapse of vasculitis. This observation demonstrates that kidney transplantation may be offered to ANCA-positive patients with end-stage renal disease due to vasculitis. However, patients under ciclosporine therapy are still at risk for the development of relapsing disease and cyclophosphamide has to be added to or substituted in part for standard immunosuppressive therapy in order to reverse clinical symptoms and prevent rapid deterioration of kidney function.

Adolescent↗
PubMed1995

Interleukin-1 beta induces the formation of nitric oxide in isolated juxtaglomerular cells: influence on renin secretion.

Renin secretion may be modulated by nitric oxide (NO). We studied whether interleukin-1 beta (IL-1 beta) induces endogenous NO synthesis in mouse juxtaglomerular cells (JGC) in primary culture, and whether endogenous NO or NO applied exogenously via sodium nitroprusside (SNP) influences renin secretion. JGC seeded on culture plates were stimulated by IL-1 beta or by SNP. Cyclic guanosine 3,5'-monophosphate (cGMP) in the cell supernatant was determined as indicator for NO effects. Stimulation of JGC with IL-1 beta or SNP increased cGMP in the supernatant significantly. The NO synthase inhibitors NG-nitro-L-arginine or NG-monomethyl-L-arginine, or the NO scavenger oxyhaemoglobin prevented the IL-1 beta-induced increase of cGMP. The biological activity of NO was shown in a bioassay by the vasodilatory effect of the effluent from an IL-1 beta-stimulated JGC column on a precontracted rat aortic ring and was prevented by oxyhaemoglobin and methylene blue. Renin activity of JGC was detected in the culture supernatants and the cells. Spontaneous renin secretion into the cell supernatant was 26 +/- 1% of total activity. Melittin or forskolin concentration dependently increased renin secretion up to 90 +/- 2%. Incubation of JGC with IL-1 beta in the absence or presence of NO inhibitors did not alter spontaneous or stimulated renin secretion. SNP (30 microM) had a dual effect on renin secretion. After 1 h of incubation, it inhibited basal renin secretion, whilst it had a stimulatory effect after 20 h of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1995

Effects of insulin-like growth factor I on phosphate transport in cultured proximal tubule cells.

In vivo, proximal tubule cells are exposed to insulin-like growth factor I (IGF-I) that is present in serum or in proximal tubule fluid. For example, in the nephrotic syndrome, proximal tubule fluid contains IGF-I at biologically meaningful concentrations in association with IGF-binding protein-2 (IGFBP-2). IGF-I has also been shown to decrease the urinary excretion of phosphate (Pi) in normal subjects. We hypothesized that IGF-I can raise tubule cell Pi absorption directly through an apical as well as a basolateral tubule receptor mechanism, specifically, through IGF-I (type I) receptors as compared to IGF-II (type II) or insulin receptors. Studies were performed in cultured proximal tubule cells that express high-affinity IGF-I receptors. Stimulation of cells selectively at the apical or basolateral membrane with IGF-I (10(-9) to 10(-7) mol/L) increases Pi absorption by up to 80%, but a significant counterdirectional Pi flux in the apical-to-basolateral direction does not occur. The effect of IGF-I on Pi transport appears to be specific inasmuch as the transport of alanine is not affected by the peptide. IGFBP-2 does not inhibit this effect of IGF-I, but the IGF-I-induced increase in Pi transport is inhibited by a neutralizing anti-IGF-I receptor monoclonal antibody. Exposure of the cells to IGF-II (10(-7) mol/L) but not to insulin selectively at the apical membrane tends to increase Pi transport, and this IGF-II effect is also blocked by the anti-IGF-I receptor antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1995

Protein loss and genetic polymorphism of apolipoprotein(a) modulate serum lipoprotein(a) in CAPD patients.

Lipoprotein(a) (Lp(a)) serum concentrations and apoprotein(a) isoforms were measured in 64 uraemic patients treated with continuous ambulatory peritoneal dialysis (CAPD) and compared with those in 155 normal controls. The mean Lp(a) values were 44 +/- 5 mg/dl (median 30 mg/dl) in CAPD patients and 22 +/- 3 mg/dl (9 mg/dl) in controls (P < 0.01). Within the most common apo(a) isoform classes, higher concentrations of Lp(a) were seen in the CAPD patients compared with the controls (P < 0.05). These results were not influenced by differences in the frequency distribution of the apo(a) isoforms. Twenty-six CAPD patients (41%) were suffering from coronary artery disease and 63% of these patients exhibited low-molecular-weight isoforms < or = S2, compared with 31% of the patients without coronary artery disease. Furthermore a positive correlation between the daily protein (r = 0.4, P = 0.02) and albumin loss (r = 0.39, P = 0.2) into the dialysis fluid and the Lp(a) serum concentration was also observed. Therefore we suggest that the elevated Lp(a) concentrations in CAPD patients are influenced by the amount of protein loss into the dialysate and by the allelic variation of the apo(a) isoform. In addition to the typical dyslipidaemia found in CAPD patients, high levels of Lp(a) and specific isoform patterns may in turn contribute to the elevated risk of coronary artery disease and other cardiovascular complications.

Adolescent↗
PubMed1995

[Atherogenic lipoprotein(a) as a progression factor in glomerular diseases: studies in cultured rat mesangial cells].

Lipoprotein abnormalities are a risk factor for atherosclerotic disease and considered to accelerate glomerular injury in kidney disease. Serum levels of Lp(a) are elevated in patients with nephrotic syndrome and Lp(a) deposits are found in diseased glomeruli. Since mesangial hypercellularity is a prominent feature in a variety of glomerular diseases, we studied the effects of Lp(a) on proliferation of cultured rat mesangial cells. DNA synthesis was stimulated in cells incubated in the presence of Lp(a) as were the mRNA levels for c-fos and c-myc, two "early genes" that serve as transcription factors. Lp(a) also accelerated cell growth by 42 +/- 6% compared to control cells. Increased DNA synthesis was partially blunted, when cells were incubated with Lp(a) in the presence of oxygen radical scavengers CAT and SOD. We conclude that Lp(a) abnormalities are likely to contribute to glomerular injury in kidney disease. The mechanism by which Lp(a) alters the proliferation rate of mesangial cells involves the formation of reactive oxygen species.

Animals↗
PubMed1995

In vitro and in vivo studies with different precipitate filter cartridges for H.E.L.P.-LDL-apheresis. Optimization of precipitate filter cartridges.

Heparin-induced extracorporeal LDL-precipitation has successfully been used in lowering high serum cholesterol in patients with coronary heart disease due to familial hypercholesterolemia. In the continuous search to improve treatment facilities we attempted to increase the filtration capacity of low density lipoprotein by the precipitate filter of the H.E.L.P.-system. Therefore, the nominal filtration area was varied by decreasing the pleat count as well as the configuration of the precipitation filter membrane. The device was tested in vitro using fresh frozen plasma from healthy donors as well as in vivo treating 6 patients suffering from familial hypercholesterolemia and 18 patients with the nephrotic syndrome. The data show that the drop in pressure on the filtration side depended on the filtration volume and the filter configuration. Reducing the pleat number and in parallel the nominal filtration area by replacing the standard support on the outside of the membrane by a double or triple thick support results in an increase in plasma volume which can be treated. The optimal results were obtained using filters with a nominal filtration area of 0.8 +/- 0.1 m2 and a triple thick support on the retention side compared to the standard configuration. Therefore, even patients with extreme plasma viscosity such as patients with the nephrotic syndrome can effectively be treated by heparin-induced LDL-precipitation.

Adult↗
PubMed1995

Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by endothelin in human glomerular epithelial cells.

The regulation of the inositide signalling pathway and [Ca2+]i by endothelin (ET) peptides was investigated in human glomerular epithelial cells in culture. Endothelin-1 and -2 induced an accumulation of inositol phosphates in a time- and dose-dependent manner. The baseline of [Ca2+]i in glomerular epithelial cells was 109 +/- 2.8 nmol/l, n = 60. Endothelin-1 (ED50: approx. 3 x 10(-9) mol/l) caused a rapid and transient rise in [Ca2+]i as detected by fura-2 microfluorimetry studies. The endothelin-1-induced inositol phosphate accumulation was inhibited by the selective ETA receptor antagonist BQ123. Endothelin-3 and BQ3020, a selective ETB receptor agonist, showed no effect. The results suggest an ETA-mediated pathway. This study demonstrates an ETA-mediated transmembrane signalling via phospholipase C with consecutive elevation of inositol phosphates and intracellular calcium. Since endothelin peptides contribute to both normal renal function and renal dysfunction, this study adds further knowledge on glomerular cell regulation.

Calcium↗
PubMed1995

Clinical utility of antilipidemic therapies in chronic renal allograft failure.

Hyperlipidemia following successful renal transplantation is a frequent and persistent disorder, and lipid abnormalities are associated with ischemic heart disease. Correlates have been found to cyclosporine and steroids as the major causes of lipid disorders. Cardiovascular disease is currently the major cause of death among renal graft recipients in the long run. Therefore, lipid lowering therapy appears to be useful in those patients without cardiovascular disease (primary prevention) and is mandatory in those with established coronary artery disease (secondary prevention). Because of the multiplicity of other cardiovascular risk factors, hyperlipidemia might only be of minor importance. On the other hand, lipids may even accelerate the development of arteriosclerosis in a preinjured vascular endothelium. Dietary modification or reduction of dietary fat is considered to be the first line of antilipemic therapy. Unfortunately, hyperlipidemia appears not to be responsive to modification of dietary fat without weight reduction. In general, patients taking immunosuppressive drugs after organ transplantation are grouped under high risk population when pharmacological intervention is selected, since only some lipid lowering drugs are safe and efficacious in short-term studies and when used with precaution. Low-dose HMG-CoA reductase inhibitor is the drug of choice for lowering LDL cholesterol. Immunosuppression withdrawal protocols have successfully been used to control massive hyperlipidemia in immunologically stable patients in the long term. Although evidence from prospective controlled intervention studies is lacking, it is reasonable to adopt the principle of a broad-based approach aimed at reducing LDL cholesterol as well as other major risk factors for cardiovascular disease in this patient population. The likelihood is that effective control of serum lipids and lipoproteins may achieve a similar beneficial reduction in absolute mortality in renal transplant recipients as already demonstrated in individuals without kidney disease but with cardiovascular damage.

Graft Rejection↗
PubMed1994

Oxidized lipoprotein(a) inhibits endothelium-dependent dilation: prevention by high density lipoprotein.

We assessed the effects of human native and oxidized lipoprotein(a) (150 min, 30 and 100 micrograms/ml) on endothelium-dependent vasodilation of isolated rabbit renal arteries. Vasodilation was not attenuated after incubation of arteries with native lipoprotein(a). However, when the arteries were exposed to oxidized lipoprotein(a), acetylcholine-induced vasodilation was dose dependently significantly impaired. Concomitant incubation of segments with high density lipoprotein (HDL, 0.5 mg/ml) prevented the attenuation of dilations induced by oxidized lipoprotein(a). Thus, we report for the first time that oxidized lipoprotein(a) impairs endothelium-dependent vasodilation, and that HDL prevents its inhibitory effect.

Acetylcholine↗