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Biomedical subjects

M Gräfe

Publications and source records attributed to M Gräfe.

11 recordsLinked to original sources
PubMed1992

Relaxation of human coronary artery and arteria mammaria by K(+)-channel openers.

Three agents with K(+)-channel-opening activity--nicorandil, bimakalim (EMD 52692), and EMD 56431--were tested for vasorelaxation abilities in human coronary artery and human arteria mammaria. The potency orders were bimakalim = EMD 56431 >> nicorandil for relaxation in human coronary artery and bimakalim = EMD 56431 >> nicorandil in human arteria mammaria. These data demonstrate that K(+)-channel openers are effective vasorelaxant agents in human coronary artery and human arteria mammaria. Bimakalim and EMD 56431 were more potent than nicorandil, a drug that also activates guanylate cyclase.

Benzopyrans↗
PubMed1992

In vivo measurement of endothelium-dependent vasodilation with substance P in man.

Endothelial cells synthesize and metabolize vasoactive substances which are involved in the regulation of vascular tone. Among these factors, the endothelium-derived nitric oxide (NO) appears to be of major importance. Many studies observed an impairment of the generation, release, or the diffusion of endothelial NO across the vascular intima in laboratory animals with various experimental diseases such as hypercholesterolemia, atherosclerosis and hypertension. In human coronary arteries obtained from explanted hearts impaired endothelium-dependent relaxations were measured in atherosclerotic segments. The hypothesis of a decreased NO mediated vasodilation in patients with coronary artery disease was further underscored by in vivo studies in man using intracoronary infusions of the endothelium-dependent vasodilator acetylcholine and quantitative coronary angiographic measurements of the diameter changes. From these observations it was assumed that endothelial dysfunction, in particular a profound inability of the coronary endothelium to relax via NO dependent mechanisms may play an important role in the pathogenesis of abnormal coronary vasomotion. However, further investigations in man reveal that the ability of the coronary endothelium of patients with coronary artery disease or vasospastic angina to produce endothelial NO is less affected as judged from the effects of acetylcholine. In recent investigations a largely preserved endothelial function could be measured in these patients when the endothelium-dependent vasodilator substance P was used as a tool for the measurement of NO dependent relaxation. Thus, endothelial dysfunction does not appear to serve as a major cause of abnormal vasoconstriction in coronary artery disease or vasospastic angina in man.

Acetylcholine↗
PubMed1992

Bradykinin degrading activity in cultured human endothelial cells.

The role of angiotensin-converting enzyme (ACE), neutral endopeptidase 24.11 (NEP), and other peptidases in the endothelial degradation of bradykinin was investigated in cultured human umbilical vein endothelial cells (HUVEC). The major part of the kininase II activity on intact cells was attributed to ACE activity, the minor part to NEP activity. Amastatin, as aminopeptidase inhibitor, and DL-2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid (MGTA), an inhibitor of kininase I, did not affect endothelial kininase activity. The decline of the bradykinin concentrations in the supernatant of intact endothelial monolayer indicated a total kininase activity of 289 +/- 27 fmol/min/dish. The calculated activity of ACE was 223 fmol/min/dish and the neutral endopeptidase activity was 51 fmol/min/dish. Thus, ACE and neutral endopeptidase are the main kininases in the degradation of bradykinin by intact endothelial cells. In contrast to the intact endothelial monolayers, in homogenates additional kininase activity was found which was not affected by either ACE and NEP inhibitors nor by amastatin and MGTA.

3-Mercaptopropionic Acid↗
PubMed1992

Local potentiation of bradykinin-induced vasodilation by converting-enzyme inhibition in isolated coronary arteries.

The interaction of angiotensin-converting enzyme (ACE) inhibitors and bradykinin was investigated in isolated bovine and human coronary arteries. Rings with and without endothelium were mounted in organ chambers for measurement of isometric force. The effects of the ACE inhibitors lisinopril, enalaprilat, fosinoprilat, ramiprilat, and captopril were determined during submaximal stimulation with bradykinin or other vasodilators. Lisinopril and captopril alone did not affect vascular tone; however, in rings with endothelium partially relaxed with bradykinin (> or = 10(-10) M), all ACE inhibitors caused further relaxations. Lisinopril did not affect bradykinin concentrations in the incubation medium. Mechanical removal of the endothelium or incubation with nitro-L-arginine or the bradykinin2-receptor antagonist Hoe 140 prevented the relaxations to bradykinin and lisinopril. Other vasodilators including acetylcholine, adenosine diphosphate, substance P, or SIN-1 did not prime the rings to respond to ACE inhibitors. Endothelium-dependent relaxations to lisinopril were also observed in human coronary arteries treated with bradykinin (> or = 10(-7) M). Thus, ACE inhibitors potentiate endothelium-dependent relaxations to submaximal concentrations of bradykinin in bovine and human coronary arteries. This local mechanism occurs regardless of elevated bradykinin concentrations in the blood and reduced angiotensin II generation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Endothelium-dependent relaxations are augmented in rats chronically treated with the angiotensin-converting enzyme inhibitor enalapril.

The study was designed to evaluate the effects of chronic inhibition of angiotensin-converting enzyme (ACE) on the reactivity of the endothelium and the smooth muscle to vasoconstrictor and vasodilator stimuli in normal rats. Male rats were treated orally for 6 weeks with enalapril (10 mg/kg/day, n = 10) or with placebo (n = 10). Endothelium-dependent relaxations to acetylcholine and adenosine diphosphate were augmented in aortic rings from rats treated with enalapril compared with controls, whereas the response to the endothelium-independent vasodilator SIN-1 were similar. Contractions induced by phenylephrine and angiotensin II remained unchanged. Thus, the results suggest that chronic ACE inhibition enhances the release of relaxing factors from the endothelium in normotensive rats.

Acetylcholine↗
PubMed1992

Effects of converting enzyme inhibition on endothelial bradykinin metabolism and endothelium-dependent vascular relaxation.

The effects of ACE-inhibitors on bradykinin metabolism and bradykinin-induced endothelium-dependent relaxation were studied in isolated coronary arteries and endothelial cells in culture. The results suggest that ACE-inhibitors affect coronary vascular tone by at least two endothelium-dependent and bradykinin-mediated mechanisms: First, ACE-inhibitors decrease endothelial bradykinin degredation which is accompanied by an augmented bradykinin mediated endothelium-dependent relaxation. Second, ACE-inhibitors evoke endothelium-dependent relaxations in coronary arteries stimulated with threshold concentrations of bradykinin, which cannot be attributed to an inhibition of bradykinin degradation. The effect appears to represent a new mechanism which may be based on an interaction of the bradykinin receptor and the angiotensin converting enzyme on the cellular level.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Endothelial protection].

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Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

[Directional atherectomy--current status].

To deal with the problem of restenosis after PTCA, several new methods and devices for treating atheromatous lesions have been developed. Among the promising techniques, is the opportunity to remove atheromatous material with the directional coronary atherectomy catheter designed by J.B. Simpson. The atherectomy catheter consists of a housing at the catheter tip with a concave cutting device which is rotated at a speed of 2000 r.p.m. The housing is positioned at the stenosis by means of a central guidewire; the material to be removed protrudes into the housing. With an inflatable balloon on the opposite side, the position of the housing is fixed in the coronary artery, the plaque is pressed further into the orifice and severed by the rotating blade. The material removed remains in the tip of the housing and can be used for morphologic examination as well as for functional studies with individual cell cultures. Experience published to date encompasses the results of 1032 treated stenoses. The majority of the treated lesions, 53%, were localized in the left anterior descending coronary artery; in 22% the lesion were located in the right coronary artery, in 17% in an aorto-coronary venous bypass graft. Due to the difficulty in positioning the relatively rigid atherectomy catheter, the method has only been employed in the circumflex artery in 6%. In a substantial number of patients, the stenoses had already been subjected to PTCA; in 57% of 963 patients treated with atherectomy, angioplasty had been performed previously, in 25% bypass grafting had been carried out. The primary success rate was 93%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Stress fibres (SF) in human endothelial cells (HEC) under shear stress.

Human umbilical veinous endothelial cells are cultured on artificial substrates precoated with extracellular matrix from bovine corneal endothelial cells. These cultural conditions help cells to keep an elevated maintenance level for otherwise unusual time intervals. Integrity of endothelial cell layers is of special interest for nondisturbed blood circulation. Therefore we look after mechanisms of cell--cell and cell--substrate--adherence. Here we focus on stress fibres, microfilaments, which seem to play an important part in cellular adherence phenomena. Since endothelial cells in vivo are constantly shear stressed by the blood stream we investigated cell--substrate interactions in vitro under dynamical conditions with the help of a modified cone--plate rheometer originally designed for hemorheology. It can be demonstrated in these shearing experiments that toxical substances influence the organization of stress fibres.

Actin Cytoskeleton↗
PubMed1975

The influence of food intake on the development of structural and functional adaptation following ileal resection in the rat.

The present study was undertaken to determine the influence of hyperphagia on the adaptive changes occurring in the rat jejunal mucosa as a result of intestinal resection. One group of resected rats was subjected to pair feeding with a sham-operated population, whilst another group was nourished ad libitum. The animals which ate ad libitum developed hypertrophy of the mucosa which was accompanied by increased glucose absorption in vivo without changes in enzyme levels. These alterations were much less pronounced in the pair-fed group of resected animals, a finding that indicates that the adaptive changes are at least partially influenced by increased luminal nutrition.

Adaptation, Physiological↗