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K Kugiyama

Publications and source records attributed to K Kugiyama.

At least 109 records · Page 6Linked to original sources
PubMed1996

Menstrual cyclic variation of endothelium-dependent vasodilation of the brachial artery: possible role of estrogen and nitric oxide.

Estrogens have been reported to influence endothelial functions. This article's aim is to examine whether endothelium-dependent vasodilation of brachial arteries is changed in parallel with the physiological variation of the ovarian hormones during the menstrual cycle in young healthy female subjects. With high-resolution ultrasonography, we measured the diameter and blood flow of brachial arteries at rest, during reactive hyperemia, and after sublingual nitroglycerin administration in 15 young healthy female subjects (mean 29.6 +/- 2.6 years). All female subjects were studied in each of three different phases of one menstrual cycle (M, menstrual phase; F, follicular phase; L, luteal phase). The increase in arterial diameter during reactive hyperemia was lowest in the menstrual phase and highest in the follicular phase (4.9 +/- 0.8% in M; 14.1 +/- 0.9% in F; 9.2 +/- 1.1% in L; p < 0.005 between any two means among the groups). No significant difference was apparent in the percentage of increase in blood flow during reactive hyperemia among the three phases. The percentage of increase in arterial diameter after nitroglycerin administration also was not significantly different among the three phases of the cycle. The serum estradiol level was lowest in the menstrual phase and was highest in the follicular phase (17.5 +/- 1.6 pg/ml in M, p < 0.0005, M versus F and L; 107.8 +/- 18.0 pg/ml in F, p < 0.05, F versus L; 74.4 +/- 7.3 pg/ml in L). The serum level of nitrite-nitrate, measured by the Griess reaction, was highest in the follicular phase and was lowest in the menstrual phase of the three different phases (40.4 +/- 7.9 mumol/l in M, p < 0.01, M versus F, and p < 0.05, M versus L; 106.7 +/- 17.6 mumol/l in F, p < 0.05, F versus L; 62.2 +/- 6.2 mumol/l in L). In conclusion, a significant variation of the endothelium-dependent vasodilation parallels the levels of serum estradiol and nitrite-nitrate during the menstrual cycle in female subjects.

Adult↗
PubMed1995

A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier.

Histochemical and electron microscopic studies were performed in an attempt to clarify the muscle pathology in an 18-year-old man with Fabry disease, showing proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes revealed by histochemistry, electron microscopy demonstrated the widespread accumulation of abundant lamellated bodies in myofibers, associated with increased glycogen granules and autophagic vacuoles. The cardiac muscle of the proband's mother revealed a mosaic pattern of normal-appearing and hypertrophic myofibers containing a number of ring-like, lamellated bodies. Although further studies are necessary to support our findings, skeletal muscle is apparently involved in patients with Fabry disease, and a mosaic pattern of cardiac muscle involvement possibly reflecting Lyonization, may be one of the characteristic findings of a Fabry disease carrier.

Adolescent↗
PubMed1995

Increased constrictor response to acetylcholine of the isolated coronary arteries from patients with variant angina.

The aim of this study was to determine whether isolated coronary arteries from patients with variant angina show hyperreactivity and/or supersensitivity to acetylcholine in vitro. Coronary arterial rings were obtained at autopsy within 3 h after death from six coronary arteries having spasm in four patients with variant angina and from 22 coronary arteries in 14 control patients with non-cardiac death. The coronary rings were suspended in the organ chamber filled with Krebs Henseleit solution bubbled with 95% O2 + 5% CO2, and their isometric tensions were monitored. Arterial rings isolated from both the patients with variant angina and the controls contracted dose-dependently in response to acetylcholine (10(-9)-10(-5) mol/l). EC50 of acetylcholine (i.e. concentration producing 50% of maximum contraction) was not significantly different between the coronary arteries from patients with variant angina and those from controls, but maximum contraction elicited by acetylcholine (expressed as a percentage of the contraction elicited by 60 mmol/l KCl) was significantly greater in the coronary arteries from patients with variant angina than those from controls. In conclusion, the isolated coronary arteries from patients with variant angina have hypercontractile reactivity to acetylcholine. This intrinsic alteration of the coronary reactivity to acetylcholine may play a role in the genesis of coronary spasm occurring in the situations of enhanced parasympathetic nervous discharge.

Acetylcholine↗
PubMed1995

Effects of brain (B-type) natriuretic peptide on coronary artery diameter and coronary hemodynamic variables in humans: comparison with effects on systemic hemodynamic variables.

OBJECTIVES: This study attempted to clarify the effects of human brain (B-type) natriuretic peptide on coronary artery diameter and coronary vascular resistance in humans. BACKGROUND: Brain natriuretic peptide induces vasodilation in systemic circulation by activating particulate guanylate cyclase of the vascular smooth muscle. METHODS: In 13 patients with normal coronary arteries and left ventricular function, brain natriuretic peptide was infused at 0.5 microgram/kg body weight per min for 4 min into the left main coronary artery (six patients, Group A) or into the pulmonary artery (seven patients, Group B). Systemic hemodynamic variables and coronary sinus blood flow were measured before and after the infusion. The lumen diameter of the left coronary artery was quantitatively measured. RESULTS: In both groups, brain natriuretic peptide significantly increased heart rate and decreased mean arterial pressure. Rate-pressure product remained unchanged in both groups. Brain natriuretic peptide decreased systemic vascular resistance index significantly in both groups (both p < 0.01 vs. baseline), and there was no difference in the effect between the groups. Brain natriuretic peptide decreased coronary vascular resistance in Group A (p < 0.01 vs. baseline) but did not affect coronary vascular resistance in Group B (p < 0.01 vs. Group A). The lumen diameters of the proximal and distal segments of the left coronary artery were increased significantly after brain natriuretic peptide in both groups. After infusion of brain natriuretic peptide, mean plasma level of brain natriuretic peptide in the coronary sinus increased from 36 to 130,411 pg/ml in Group A and from 64 to 12,329 pg/ml in Group B. CONCLUSIONS: Brain natriuretic peptide shows a vasodilator effect on the coronary artery system in humans. However, the effect does not appear uniformly but is seen preferentially in the epicardial coronary artery. The sensitivity of the coronary resistance vessels to brain natriuretic peptide is low compared with that of the resistance vessels of the systemic circulation.

Cardiac Catheterization↗
PubMed1995

Comparison of secretion pattern between A-type and B-type natriuretic peptides in patients with old myocardial infarction.

OBJECTIVES: The present study was designed to compare the secretion patterns of two cardiac hormones--A-type (atrial) and B-type (brain) natriuretic peptides--from the ventricles in patients with old myocardial infarction. BACKGROUND: Plasma levels of these two natriuretic peptides are increased, and their secretion from the ventricles is augmented, in patients with congestive heart failure. METHODS: We measured the plasma levels of these two types of natriuretic peptides at the aortic root and the anterior interventricular vein in 42 patients with old myocardial infarction (anterior in 22 and inferior in 20) and 18 control subjects. RESULTS: The difference between the plasma levels of both A- and B-type natriuretic peptide in the anterior interventricular vein and aortic root was significantly greater in the groups with anterior and inferior infarction than in the control group (A-type [mean +/- SD] 380 +/- 290 and 247 +/- 205 pg/ml in the infarction groups vs. 11 +/- 14 pg/ml; B-type 497 +/- 445 and 75 +/- 73 pg/ml vs. 23 +/- 16 pg/ml, respectively). The difference between the plasma levels of each peptide at the anterior interventricular vein and aortic root had a significant negative linear correlation with left ventricular ejection fraction in both groups with infarction. The slope of the regression line of the arteriovenous difference of B-type natriuretic peptide at the anterior interventricular vein was significantly steeper in the anterior than in the inferior infarction group (left ventricular ejection fraction -12.801 vs. -1.891, p < 0.01). CONCLUSIONS: These results indicate that 1) the secretion of A- and B-type natriuretic peptide from the left ventricular increases in proportion to the severity of left ventricular dysfunction, and 2) secretion of B-type natriuretic peptide is much greater from the infarct than from the noninfarct region, suggesting that the regional ventricular wall stretch caused by infarction strongly stimulates secretion of B-type natriuretic peptide.

Atrial Natriuretic Factor↗
PubMed1995

Lipoproteins regulate C-type natriuretic peptide secretion from cultured vascular endothelial cells.

We have shown that oxidized low-density lipoprotein (Ox-LDL) modulates various endothelial cell (EC) functions. C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family to be discovered, is secreted from peripheral vascular ECs and regulates body fluid homeostasis, vascular tone, and vascular growth. This study was designed to investigate the effects of lipoproteins on CNP secretion from cultured ECs. Treatment of bovine carotid ECs with OX-LDL and its extracted lipids resulted in a concentration-dependent suppression of the spontaneous and transforming growth factor-beta 1-stimulated secretion CNP. Native LDL, its extracted lipids, and acetylated LDL were inactive. OX-LDL depleted of its amphiphilic lipids, which was prepared by incubation with defatted albumin, lost its suppressive effect on CNP secretion. 7-Ketocholesterol, one of the amphiphilic lipids in OX-LDL that is transferable from OX-LDL to defatted albumin, suppressed CNP secretion by ECs, thus mimicking the effect of OX-LDL. Coincubation with high-density lipoprotein (HDL), which alone had no effect on CNP release, significantly prevented OX-LDL-induced inhibition of CNP secretion by ECs. Analysis by thin-layer chromatography demonstrated that oxysterols, including 7-ketocholesterol, in OX-LDL were transferred from OX-LDL to HDL during coincubation of these two lipoproteins. These results indicate that OX-LDL suppresses CNP secretion from ECs by 7-ketocholesterol or other transferable hydrophilic lipids in OX-LDL, and the suppressive effect of OX-LDL is reversed by HDL. Lipoproteins thus may regulate CNP secretion from the endothelium of atherosclerotic arteries.

Animals↗
PubMed1994

Influence of exercise-induced coronary artery spasm on thallium-201 initial distribution and washout kinetics in patients with variant and classic angina pectoris.

Thallium-201 single-photon emission computed tomography was performed immediately, and 2 and 4 hours after exercise-induced anginal attack in 2 groups of patients with either exercise-induced coronary spasm or severe fixed stenosis on the isolated proximal left anterior descending coronary artery. All patients with variant angina had transient ST-segment elevation during the exercise-induced attack for thallium-201 scintigraphic study. Both perfusion defects and 4-hour washout abnormalities were significantly greater in patients with variant angina than in those with stable effort angina (p < 0.01). In patients with stable effort angina, thallium-201 activity in ischemic regions (as a percentage of initial count in the normal region) progressively decreased, whereas in patients with variant angina it increased from 38% (initial) to 48% (2 hours), and then declined to 42% (4 hours). The initial normalized thallium-201 activity in the ischemic regions was significantly lower in patients with variant angina than in those with stable effort angina (p < 0.001). In conclusion, perfusion and washout abnormalities during exercise-induced angina are greater in patients with variant angina than in those with stable effort angina. Exercise-induced coronary spasm seems to contribute to the profound reduction in initial thallium-201 distribution and delayed thallium-201 accumulation in the ischemic region.

Adult↗
PubMed1994

Comparison of the distribution of myocardial blood flow between exercise-induced and hyperventilation-induced attacks of coronary spasm: a study with thallium-201 myocardial scintigraphy.

Exercise and hyperventilation tests are often used as the provocative tests for coronary artery spasm. To examine the distribution of myocardial blood flow during exercise-induced and hyperventilation-induced attacks of coronary spasm, thallium-201 myocardial scintigraphy was performed in 47 patients with variant angina. The extent and severity scores and severity index (severity score/extent score) of scintigraphic perfusion defect were calculated. In 32 patients, anginal attack associated with ST elevation on the electrocardiogram was induced by exercise; in 23 patients, the attack was induced by hyperventilation. In patients with either anterior or inferior wall ischemia, both the extent and severity scores and severity index in the scintigram were significantly greater in exercise-induced anginal attack than those in hyperventilation-induced attack. In patients with simultaneous anterior and inferior wall ischemia, they tended to be greater in exercise-induced attack. In eight patients in whom anginal attack was induced by both exercise and hyperventilation, these scores and index were significantly greater in exercise-induced attack than those in hyperventilation-induced attack. These data suggest that myocardial ischemia during exercise-induced attack is enhanced as compared with that during hyperventilation-induced attack. Thallium-201 scintigraphy combined with exercise testing seems to be more sensitive for detecting myocardial ischemia induced by coronary spasm.

Aged↗
PubMed1994

Cigarette smoke extract contracts isolated porcine coronary arteries by superoxide anion-mediated degradation of EDRF.

To test whether cigarette smoke extract (CSE) influences the endothelial regulation of vascular tone in vitro, pig coronary arterial rings were incubated in organ chambers and isometric tension changes were examined. CSE was prepared by bubbling mainstream smoke of one filter cigarette into phosphate-buffered saline (2 ml). Fresh CSE (3.3, 10, and 30 microliters/ml) elicited initial contraction and subsequent relaxation during stable contraction to prostaglandin F2 alpha (PGF2 alpha). Initial contraction to CSE was dependent on the presence of endothelium, whereas subsequent relaxation was endothelium independent. Initial contraction was significantly attenuated by superoxide dismutase (SOD), methylene blue, but not by catalase. Prior inhibition of the basal release of endothelium-derived relaxing factor by NG-monomethyl-L-arginine also inhibited the initial contraction, and this inhibition was reversed by coincubation with L-arginine but not D-arginine. Subsequent relaxation was significantly potentiated by SOD but was markedly attenuated by methylene blue. CSE reduced ferricytochrome c, and this reduction was significantly inhibited by SOD. In conclusion, CSE induced biphasic tension change, initial contraction, and subsequent relaxation during stable contraction to PGF2 alpha in isolated pig coronary arteries. The initial contraction may be, at least in part, mediated through the degradation of basally released endothelium-derived relaxing factor (nitric oxide) by superoxide anions derived from CSE.

Animals↗
PubMed1994

LPC in oxidized LDL elicits vasocontraction and inhibits endothelium- dependent relaxation.

Oxidized low-density lipoprotein (ox-LDL) plays an important role in the development of atherosclerosis and potentially influences the endothelial regulation of vasomotor tone. We have recently shown that lysophosphatidylcholine (LPC), a lysophospholipid contained in ox-LDL, has various pathophysiological effects. We further examined the role of LPC in the ox-LDL-induced vasoactivity in isolated pig coronary arteries. Copper-induced ox-LDL but not native LDL (n-LDL) elicited endothelium-dependent contraction during plateau contraction evoked by prostaglandin F2 alpha. Lipid extracted from ox-LDL (ox-LDL-lipid) also induced vasocontraction, but lipid of n-LDL (n-LDL-lipid) did not influence tone. When LPC was depleted from ox-LDL (i.e., defatted albumin- or phospholipase B-treated ox-LDL), vasocontraction was significantly attenuated. Synthetic palmitoyl LPC also induced endothelium-dependent vasocontraction, mimicking the response elicited by ox-LDL, but phosphatidylcholine, which exists in n-LDL and is converted to LPC during oxidative modification of LDL, did not influence the tone. Contraction to either ox-LDL or LPC was significantly attenuated by NG-monomethyl-L-arginine but not by indomethacin or superoxide dismutase. Forty minutes of incubation of coronary rings with either ox-LDL or LPC significantly attenuated endothelium-dependent vasorelaxation to thrombin without affecting vasorelaxation to endothelium-independent vasodilator nitroglycerin. In conclusion, LPC contained in lipid fraction of ox-LDL caused endothelium-dependent contraction and inhibited endothelium-dependent relaxation in isolated pig coronary arteries. The vasocontraction might be at least in part caused by LPC-mediated inhibition of endothelium-derived nitric oxide release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure.

BACKGROUND: B-type or brain natriuretic peptide (BNP) is a novel natriuretic peptide secreted from the heart that forms a peptide family with A-type or atrial natriuretic peptide (ANP), and its plasma level has been shown to be increased in patients with congestive heart failure. This study was designed to examine the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure. METHODS AND RESULTS: We measured the plasma levels of BNP as well as ANP in 16 patients with dilated cardiomyopathy (11 men and 5 women; mean age, 59 years) and 18 control subjects (9 men and 9 women; mean age, 54 years) by sampling blood from the femoral vein, the aortic root, the anterior interventricular vein (AIV), and the coronary sinus using the newly developed immunoradiometric assay systems. In the control subjects, there was no significant difference in the plasma ANP level between the aortic root and the AIV (24.0 +/- 5.2 pg/mL versus 32.2 +/- 17.0 pg/mL), but there was a highly significant step-up of the level between the AIV and the coronary sinus (32.2 +/- 17.0 pg/mL versus 371.4 +/- 111.1 pg/mL, P < .001). In contrast, there was a significant step-up of the plasma BNP level between the aortic root and the AIV (8.6 +/- 6.4 pg/mL versus 19.0 +/- 11.5 pg/mL, P < .01) but not between the AIV and the coronary sinus (19.0 +/- 11.5 pg/mL versus 28.8 +/- 14.0 pg/mL). On the other hand, in patients with dilated cardiomyopathy, there was a significant step-up in the plasma ANP level between the aortic root and the AIV (280.6 +/- 183.7 pg/mL versus 612.3 +/- 431.6 pg/mL, P < .01) and between the AIV and the coronary sinus (612.3 +/- 431.6 pg/mL versus 1229.0 +/- 772.7 pg/mL, P < .01). There was a significant step-up in the plasma BNP level between the aortic root and the AIV (268.4 +/- 293.2 pg/mL versus 511.6 +/- 458.1 pg/mL, P < .01) but not between the AIV and the coronary sinus (511.6 +/- 458.1 pg/mL versus 529.7 +/- 455.3 pg/mL) in patients with dilated cardiomyopathy. The arteriovenous difference at the AIV of the plasma level of BNP had a significant positive correlation with left ventricular end-systolic volume index (r = 0.859, P < .001) and a significant negative correlation with left ventricular ejection fraction (r = -.735, P < .001). CONCLUSIONS: We conclude that (1) BNP is secreted mainly from the left ventricle in normal adult humans as well as in patients with left ventricular dysfunction, whereas ANP is secreted from atria in normal adult humans and also from the left ventricle in patients with left ventricular dysfunction; (2) secretion of BNP as well as ANP from the left ventricle increases in proportion to the severity of the left ventricular dysfunction, suggesting that the secretions of ANP and BNP from the left ventricle are regulated mainly by wall tension of the left ventricle; and (3) the peripheral plasma levels of ANP and BNP reflect the secretion rate of these hormones from the left ventricle and may be used as a marker of the degree of left ventricular dysfunction in patients with left ventricular dysfunction.

Aged↗
PubMed1994

Lysophosphatidylcholine in oxidized low-density lipoprotein increases endothelial susceptibility to polymorphonuclear leukocyte-induced endothelial dysfunction in porcine coronary arteries. Role of protein kinase C.

We have shown that transferred lysophosphatidylcholine (lysoPC) from oxidized low-density lipoprotein (Ox-LDL) to endothelial surface membrane activates protein kinase C (PKC) in endothelial cells, suggesting that Ox-LDL could alter endothelial functions through PKC activation. The purposes of the present study were to examine whether the endothelial susceptibility to polymorphonuclear leukocytes (PMNs) may be altered in Ox-LDL-treated coronary arteries, which have properties closely resembling those observed in atherosclerotic arteries, and to determine the mechanism(s) by which Ox-LDL may affect the endothelial susceptibility to PMNs. Isolated porcine coronary arteries were cannulated and perfused with oxygenated culture medium with or without LDLs or lipids at a constant flow (37 degrees C, pH 7.4). The treatment of porcine coronary arteries with Ox-LDL increased endothelial adhesiveness to PMNs and augmented PMN-induced impairment of endothelium-dependent arterial relaxation (EDR). Furthermore, Ox-LDL stimulated the expression of intercellular adhesion molecule-1 (ICAM-1) in the porcine coronary arterial endothelium. These effects of Ox-LDL were not mediated by the scavenger-receptor-mediated process but were attributed to lysoPC in Ox-LDL. Blocking of the PMN adherence to endothelium by using anti-CD18 monoclonal antibody abolished the PMN-induced impairment of EDR. Coincubation with staurosporine or calphostin C, inhibitors of PKC, during treatment of the arteries with Ox-LDL or lysoPC attenuated the augmentative effects of Ox-LDL and lysoPC on endothelial ICAM-1 expression, endothelial adhesiveness to PMNs, and PMN-induced EDR impairment. Treatment of the arteries with phorbol 12-myristate 13-acetate, a potent stimulator of PKC, induced ICAM-1 expression and enhanced the endothelial adhesiveness to PMNs and PMN-induced EDR impairment, mimicking the effects of Ox-LDL. These results suggest that lysoPC in Ox-LDL induces endothelial ICAM-1 expression, which facilitates PMN adherence to endothelium and the subsequent augmentation of PMN-induced EDR impairment. PKC activation in endothelial cells by lysoPC in Ox-LDL may at least in part be involved in these effects of Ox-LDL. LysoPC in Ox-LDL increases endothelial susceptibility to PMN-induced endothelial dysfunction.

Animals↗
PubMed1994

[Antianginal drugs].

Explore the source record for details and available documents.

Adrenergic beta-Antagonists↗
PubMed1993

Contraction and endothelium dependent relaxation via alpha adrenoceptors are variable in various pig arteries.

OBJECTIVE: The aim was to examine differences in the vascular response to alpha adrenoceptor stimulation on both smooth muscle and endothelium among large arteries perfusing various organs. METHODS: In ring preparations of coronary, carotid, iliac, mesenteric, and renal arteries from pigs (n = 24), the magnitudes of contraction to noradrenaline (with beta blocker), with or without endothelium, and endothelium dependent relaxation to noradrenaline (with alpha 1 and beta blocker) were compared in vitro. RESULTS: In both endothelium-intact and denuded groups, the contractions to noradrenaline were significantly smaller in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. The presence of endothelium significantly suppressed the contractions in coronary and carotid arteries, but did not affect the contractions in iliac, mesenteric, and renal arteries. The endothelium dependent relaxations to noradrenaline, which were abolished by LNMMA, were more prominent in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. CONCLUSIONS: The contractions via alpha adrenoceptors were small, and endothelium dependent relaxations via alpha 2 adrenoceptors were large, in the coronary and carotid arteries, which perfuse the vital organs (heart and brain), as compared with those in iliac, mesenteric, and renal arteries. These results suggest that in the state of activation of the sympathetic nervous system, arterial tone in response to alpha adrenoceptor stimulation may be regulated not only by alpha adrenoceptors on vascular smooth muscle but also by those on endothelium, through release of endothelium derived relaxing factor (EDRF) via alpha 2 adrenoceptors.

Animals↗
PubMed1993

Activated human polymorphonuclear leukocytes elicit endothelium-dependent contraction in isolated pig coronary arteries.

Interaction between activated human polymorphonuclear leukocytes (PMNL) and endothelial regulation of isolated pig coronary artery tone was examined. PMNL were isolated from venous blood of healthy human volunteers. Pig coronary artery rings were incubated in an organ chamber, and isometric tension changes induced by opsonized zymosan (1 mg/ml)-activated PMNL were examined. Activated PMNL elicited dose-dependent contraction (maximum value 45.9 +/- 4.1% of precontraction, mean +/- SEM] in prostaglandin F2 alpha (PGF2 alpha)-precontracted rings. The contraction was markedly attenuated by superoxide dismutase (SOD 100 U/ml) to 9.9 +/- 2.4% (p < 0.001), but not by catalase (1,000 U/ml). After inhibition of basal production of endothelium-derived relaxing factor (EDRF) (nitric oxide, NO) by endothelial removal or by treatment of an inhibitor of NO synthase, NG-monomethyl-L-arginine (L-NMMA), PMNL also failed to induce the contraction. A 5-lipoxygenase inhibitor (AA-861) and a cyclooxygenase inhibitor (indomethacin) did not alter the contraction to activated PMNL significantly. Time course of oxygen free radical release from PMNL measured by luminol-dependent chemiluminescence was closely synchronized with that of the endothelium-dependent contraction elicited by PMNL. In each preparation of PMNL, the maximum luminescence count and the maximum contraction induced by activated PMNL showed significant positive correlation quantitatively (r = 0.958, p < 0.001). Activated human PMNL elicited endothelium-dependent contraction in isolated pig coronary arteries. The contraction may be mediated through inactivation of basal production of EDRF (NO) by superoxide anions released from PMNL.

Animals↗
PubMed1993

Protein kinase C inhibitors prevent impairment of endothelium-dependent relaxation by oxidatively modified LDL.

The mechanism(s) of inhibition of endothelium-dependent relaxation (EDR) by oxidized low-density lipoprotein (Ox-LDL) was examined in isolated porcine coronary arteries and rabbit aortas. Incubation with Ox-LDL but not native LDL caused the inhibition of thrombin- or acetylcholine-induced EDR, whereas A23187-induced EDR was preserved after incubation with Ox-LDL. Lysophosphatidylcholine (lysoPC), which was abundant in Ox-LDL and was found to be transferred from Ox-LDL to endothelial cells, also caused the inhibition of EDR in response to thrombin or acetylcholine but not to A23187. Ox-LDL depleted of lysoPC, which was prepared by phospholipase B, failed to inhibit the vasorelaxation. Coincubation with staurosporine or calphostin C, potent inhibitors of protein kinase C, attenuated the EDR inhibition by Ox-LDL or lysoPC. Phorbol 12-myristate 13-acetate, a specific protein kinase C activator, caused the EDR inhibition, and its effect was attenuated by staurosporine or calphostin C. Furthermore, lysoPC was capable of activating protein kinase C purified from cultured porcine endothelial cells. In conclusion, protein kinase C activation plays a role in the inhibition of surface receptor-mediated EDR by Ox-LDL, and lysoPC transferred from Ox-LDL to endothelial cells may be involved in the activation of protein kinase C.

Animals↗
PubMed1993

Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta.

Exposure of isolated arteries to oxidatively modified low density lipoprotein (LDL) has been reported to suppress endothelium-dependent relaxation (EDR). To determine whether lipid degradation products in oxidized LDL contribute to impaired relaxation, we have tested the responsiveness of isolated rabbit aortas to endothelium-dependent relaxants (acetylcholine, ATP, and calcium ionophore A23187) and nitroglycerin before and after 2-hour incubations with selected lipids and LDL preparations. Concentrations (10 microM) of lecithin, phosphatidylserine, lysophosphatidylserine, sphingomyelin, phosphatidic acid, palmitate, arachidonate, and auto-oxidized arachidonate had no effect on EDR. Concentrations (10 microM) of lysolecithin, lyso-platelet activating factor, and sphingosine significantly suppressed endothelium-dependent relaxation. Native LDL (100 micrograms/ml incubation buffer) containing only small amounts of lysophosphatidylcholine exerted no effect on EDR. In contrast, LDL preparations oxidatively modified by exposure to cultured endothelial cells or copper inhibited EDR. When modified LDL was depleted of its lysolecithin by treatment with a selective phospholipase B (lysolecithinase), the inhibitory effects were attenuated. In contrast, native LDL accumulating lysolecithin under the influence of a phospholipase A2 (lecithinase) exerted inhibitory effects mimicking those of oxidized LDL. Lipids and lipoproteins had no effect on the responsiveness to nitroglycerin, an endothelium-independent vasodilator. We conclude that lysolecithin in oxidatively modified LDL contributes importantly to its vasomotor effects.

Animals↗