Biomedical subjects

Helmut Heinle

Publications and source records attributed to Helmut Heinle.

8 recordsLinked to original sources

PubMed2006

Increased gene expression of scavenger receptors and proinflammatory markers in peripheral blood mononuclear cells of hyperlipidemic males.

Interactions between peripheral blood mononuclear cells (PBMCs) and those within plaques are suggested to be pathophysiologically relevant to lipid-induced arteriosclerosis. In this study, gene expressions of scavenger receptors (CD36, CD68), LPS receptor (CD14), proinflammatory (tumor necrosis factor alpha [TNFalpha], CD40, interleukin-1 beta [IL-1beta]) and oxidative stress-related (manganese superoxide dismutase [MnSOD]) markers were analyzed in PBMCs of clinically asymptomatic males with classical proatherogenic risk factors such as smoking and/or hyperlipidemia. PBMCs were isolated from venous blood of normolipidemic non-smokers (n = 10) and smokers (n = 8), and hyperlipidemic non-smokers (n = 9) and smokers (n = 8). RNA from PBMCs was used for PCR analyses. Plasma concentrations of oxidized low-density lipoproteins (oxLDL) were measured by ELISA. The gene expressions of CD36, CD68, CD40, TNFalpha, and MnSOD were significantly higher in PBMCs of hyperlipidemics than in normolipidemics, irrespective of whether they were smoking or not. The individual expression of these genes showed significant positive correlations with each other but also with serum cholesterol or plasma oxLDL concentrations. The higher expressions of scavenger receptors, proinflammatory and oxidative stress-related genes of PBMCs are suggested to result mainly from hyperlipidemia and the accompanied increase of oxLDL concentrations.

Adult↗

PubMed2006

The mechanism of endothelium-independent relaxation induced by the wine polyphenol resveratrol in human internal mammary artery.

Resveratrol, a stilbene polyphenol found in grapes and red wine, produces vasorelaxation in both endothelium-dependent and endothelium-independent manners. The mechanisms by which resveratrol causes vasodilatation are uncertain. The aim of this study was to investigate the mechanism(s) of endothelium-independent resveratrol-induced vasorelaxation in human internal mammary artery (HIMA) obtained from male patients undergoing coronary artery bypass surgery and to clarify the contribution of different K+ channel subtypes in resveratrol action in this blood vessel. HIMA rings without endothelium were precontracted with phenylephrine. Resveratrol induced a concentration-dependent relaxation of the HIMA. A highly selective blocker of ATP-sensitive K+ channels, glibenclamide, as well as nonselective blockers of Ca2+-sensitive K+ channels, tetraethylammonium and charybdotoxin, did not block resveratrol induced relaxation of HIMA rings. 4-Aminopyridine (4-AP), non selective blocker of voltage gated K+ (KV) channels, and margatoxin that inhibits KV1.2, KV1.3, and KV1.6 channels abolished relaxation of HIMA rings induced by resveratrol. In conclusion, we have shown that resveratrol potently relaxed HIMA rings with denuded endothelium. It seems that 4-AP- and margatoxin-sensitive K+ channels located in smooth muscle of HIMA mediated this relaxation.

4-Aminopyridine↗

PubMed2006

Analysis of vasoreactivity of isolated human radial artery.

Radial artery (RA) is increasingly used as graft for coronary artery bypass grafting due to its good long-term patency. However, the mechanism of peri- and post-operative spasm is still unclear. Because of that, the aim of our study is to analyze the contractility of RA and to determine whether the presence of functional endothelium alters its contractile properties. Contractions of isolated RA rings were provoked by exogenously applied vasoconstrictors or by electrical field stimulation (EFS, 20 Hz). The order of vasoconstrictors potency based on their EC50 values was as follows: angiotensin II > phenylephrine > 5-hydroxytriptamine. Presence of endothelium increased both EC50 and maximal contraction to phenylephrine and angiotensin II, but inhibited reactivity of RA to 5-hydroxytriptamine. Spontaneous rhythmic contractions (SRC, <4 mHz) and EFS-induced contractions of RA are endothelium-independent and weaker than contractions induced by exogenously applied vasoconstrictors. Our study concludes that RA shows marked sensitivity and reactivity to angiotensin II, phenylephrine, and 5-hydroxytriptamine. Further investigations are necessary to answer why angiotensin II and phenylepehrine induce stronger contractions in the presence of endothelium. In addition, SRC as well as contractions of neurogenic origin may take part in developing vascular spasm of RA.

Angiotensin II↗

PubMed2006

Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol.

Resveratrol, a phenolic substance present in grapes and a variety of medical plants, has been reported to induce vasorelaxation, however the mechanisms are uncertain. In this paper we investigate the possible participation of K(+) channels in the endothelium-independent vasodilatation of rat aorta induced by resveratrol. Resveratrol induced concentration-dependent relaxation of rings with endothelium and without endothelium. We used different potassium channel inhibitors to determine whether the K(+) channels mediated endothelium-independent relaxation of rat aorta induced by resveratrol. Highly selective blocker of ATP-sensitive K(+) channels, glibenclamide, as well as non-selective blockers of K(+) channels, tetraethylammonium, did not block resveratrol-induced relaxation of rat aortic rings. Charybdotoxin, a blocker of calcium-sensitive K(+) channels did not affect the resveratrol-induced relaxation. 4-Aminopiridine, non-selective blocker of voltage-gated K(+) (Kv) channels, and margatoxin that inhibits Kv1 channels abolished relaxation of rat aortic rings induced by resveratrol. In conclusion, we have shown that resveratrol potently relaxed rat aortic rings with denuded endothelium. It seems that 4-aminopiridine and margatoxin-sensitive K(+) channels located in the smooth muscle of rat aorta mediated this relaxation.

4-Aminopyridine↗

PubMed2005

Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model.

Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer. Adult male rabbits were fed with lipid rich food (cholesterol: 1.3%, peanut oil: 8%) for 8 weeks. During this period MPO-inhibitors were also given (4-aminobenzoicacid-hydrazide/ABAH/-13.3 mg/kg/day or indometacin-5 mg/kg/day). All animals developed intimal lipid plaques (raised fatty streaks). The relative plaque-covered areas of the aortas were compared and the media thickness of the aorta was measured on plaque-free as well as plaque-containing areas. The medial smooth muscle density and peroxidase activity of the aortic media were also determined. The media thickness increased (p<0.05) in the cholesterol+ABAH as well as in the cholesterol+indometacin groups up to 375.7 (+/-60.5) and 442.5 (+/-123.4) microm, respectively, compared to the control group (cholesterol feeding alone) where it measured only 308.4 (+/-51.67) microm. The medial peroxidase activity decreased significantly in the indometacin treated group and showed a decreasing tendency using ABAH. In parallel to this there was a tendency of increase in the relative plaque covered areas. The smooth muscle density showed no significant modifications, while inhibitors of the MPO seemed to enhance aortic medial thickness, i.e. the grade of a pre-atherosclerotic lesion, in our animal model. Collectively, the anti-atherogenic effect of certain steroid hormones might be realized through the impact on MPO activity.

Aniline Compounds↗

PubMed2004

Thin-layer chromatography and multivariate data analysis of willow bark extracts.

In most cases the pharmacological activity of plant extracts is not assigned to single components and often not all active ingredients are known. Approaches other than those considering single compounds only to analyze plant material have proven helpful for a better characterization of extracts in their entirety. In this study extracts of willow bark are analyzed by high-performance thin-layer chromatography (HPTLC) and two different pharmacological tests [the 2,2'-azobis (2-amidinopropane) dihydrochloride reaction and the xanthine/xanthine oxidase reaction] with the help of multivariate data analysis. Described are two models using the results of the chromatographic study of 22 various extracts of willow bark and their pharmacological properties. The chromatographic data are obtained by a special TLC scanner that enables measurement of HPTLC tracks simultaneously in the range of lambda = 200-400 nm. Additionally, the developed models are used to predict the activity of another three extracts of willow bark demonstrating the quality of the model.

Chromatography, Thin Layer↗

PubMed2002

Modulation of the beta-adrenergic receptor system of vascular smooth muscle cells in vitro and in vivo by chronically elevated endothelin-1 levels.

Endothelin-1 (ET-1) levels are chronically elevated in several cardiovascular diseases and correlate with an increased mortality. However, in contrast to acute biological activities such as vasoconstriction, little is known about long-term effects of ET-1. In this study we determined the effects of ET-1 on the beta(2)-adrenergic receptor (AR) system. Incubation of smooth muscle cells with ET-1 for 72 hr led to increased beta(2)AR density as determined by radioligand binding. Experiments with inhibitors of protein and RNA synthesis as well as RT-PCR revealed that beta(2)AR upregulation required de novo synthesis. In addition, protein kinase C but neither NO nor prostaglandin metabolism were involved in this effect. The enhanced expression of beta(2)AR was associated with an increased expression of its stimulatory G-protein and the receptor's ability to stimulate adenylyl cyclase. To study chronic effects of ET-1 in vivo, rats were infused with ET-1 for 3 weeks. Similarly as in cultured cells, prolonged ET-1 exposure led to increased betaAR expression in vivo. As a consequence, beta(2)AR-induced vasodilatation was increased in aortic rings from ET-1-treated animals. Our results therefore suggest that chronically elevated ET-1 levels in vitro and in vivo induce counterregulatory mechanisms by increasing betaARs that attenuate the vasoconstrictive effects of ET-1.

Adenylyl Cyclases↗

PubMed2002

Comparison of the effects of alpha-tocopherol, ubiquinone-10 and probucol at therapeutic doses on atherosclerosis in WHHL rabbits.

Oxidative modification of lipoproteins may trigger and maintain atherogenesis. We compared the effects of different antioxidants (alpha-tocopherol, probucol, ubiquinone-10) at doses similar to those used in humans in Watanabe Heritable Hyperlipidemic (WHHL) rabbits for 12 months. Aortic lesions were analyzed for their extent and cellular composition of lesions, mean thickness of fibrous caps and density of smooth muscle cells therein, content of antioxidants, non-oxidized and oxidized lipids. Compared to controls, probucol significantly lowered the extent and macrophage content of lesions and increased the existence and smooth muscle cell density of fibrous caps. alpha-Tocopherol supplementation increased the aortic content of vitamin E, but had no decreasing effect on either the accumulation of macrophage-specific antigen in the aorta or lesion size. Nevertheless, both probucol and alpha-tocopherol significantly decreased in vitro LDL oxidizability, measured under typically strong oxidative conditions. Ubiquinone-10 supplement increased lesion size and the fraction of lesions containing fibrous caps; however, LDL oxidizability remained unaffected by ubiquinone-10 treatment. None of the antioxidants tested lowered oxidized lipids within aortic tissue; however, long-term treatment with probucol provided the most effective anti-atherosclerotic effect, while alpha-tocopherol may be pro-atherogenic and ubiquinone-10 exerts ambivalent effects. Our data suggest that (i) widely used oxidation measures, such as ex-vivo LDL oxidizability, do not reflect the degree of atherosclerosis; and (ii) long-term beneficial effects of relatively low doses of antioxidants may be outweighed by high levels of plasma cholesterol in WHHL rabbits.

Animals↗