Effects of hypercholesterolemia on the contractions to angiotensin II in the isolated aorta and iliac artery of the rabbit: role of arachidonic acid metabolites

The aim of this study was to investigate the effect of hypercholesterolemia on the angiotensin II-induced contractions in the isolated aorta and iliac artery of the rabbit, with respect to the role of arachidonate metabolites. Furthermore, the effect of the angiotensin-converting enzyme inhibitor ramipril was studied on the responses to angiotensin II in the cholesterol-fed rabbit. After 12 weeks of cholesterol diet (0.3%), endothelium-dependent relaxations to acetylcholine were significantly fewer compared with control (30.2 +/- 5.9% vs. 73.0 +/- 1.7%) in the aorta but not in the iliac artery of the rabbit. The angiotensin II- and methoxamine-induced contractions were also significantly lower compared with control in the aorta (101.4 +/- 6.7% vs. 60.9 +/- 4.2% and 160.2 +/- 5.7% vs. 135.8 +/- 8.0%, respectively) but not in the iliac artery. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) selectively attenuated the angiotensin II-induced contractions in rabbit aortic rings from the control group only in the presence of the endothelium, whereas it had no effect on the responses to angiotensin II in the cholesterol group (with or without endothelium). In the iliac artery, NDGA inhibited the responses to angiotensin II in both the control and cholesterol groups. Treatment with ramipril (0.33 mg/kg/day) significantly improved the maximal angiotensin II-induced contraction in the aorta of rabbits fed a cholesterol diet for 16 weeks to 61.0 +/- 7.3% (vs. 32.7 +/- 9.0% in the cholesterol group). We conclude that hypercholesterolemia leads to a reduction of angiotensin II-induced contractions in the aorta and not in the iliac artery of the rabbit. This reduction might be related to loss of endothelium-dependent lipoxygenase products and is partially reversed by ramipril.     

Taurine accelerates the regression of hypercholesterolemia in stroke-prone spontaneously hypertensive rats

The effects of taurine on the regression of pre-established hypercholesterolemia were examined in stroke-prone spontaneously hypertensive rats (SHRSP). Hypercholesterolemia was induced by feeding a hypercholesterolemic diet to SHRSP for 30 days. Then, the diet was switched to normal chow with or without 3% taurine, and the effects were followed up for another 30 days. During regression serum cholesterol level was rapidly decreased, and was accelerated by taurine. A similar accelerated decrease in cholesterol content by taurine was seen also in tissues including the liver, intestine, and aorta. In the liver, acyl-CoA:cholesterol acyltransferase (ACAT) activity was significantly low in the taurine-supplemented group, parallel with the hepatic cholesteryl ester content. On the other hand, hepatic cholesterol 7 alpha-hydoxylase activity maintained a higher level in the taurine-supplemented group. These results showed that taurine accelerates the regression of hypercholesterolemia, and suggested that this effect is related to the increase in cholesterol catabolism to bile acid through the enhancement of 7 alpha-hydoxylase activity.     

Treatment of murine cytomegalovirus salivary-gland infection by combined therapy with ganciclovir and thymic humoral factor gamma 2

Reactivity of aortic and carotid strip from control; hypertensive; hypercholesterolemic; and hypertensive/hypercholesterolemic rabbits were studied. Maximal stress was less in strips from hypertensive/hypercholesterolemic animals. Norepinephrine sensitivity was increased in the carotid artery from hypertensive/hypercholesterolemic animals (EC50: 0.11 microM; 0.35 microM control). CaCl2 sensitivity during norepinephrine-induced contractions was enhanced by hypertension and hypercholesterolemia (carotid EC50: 0.10 mM; 0.38 mM control; aorta EC50: 0.12 mM; 0.82 mM control). Similar results were obtained during membrane depolarization. 5-hydroxytryptamine sensitivity (EC50: 0.15 microM carotid; 0.18 microM aorta) was decreased during hypertension (EC50: 0.51 microM carotid; 1.13 microM aorta) and by hypercholesterolemia (EC50: 1.76 microM carotid; 1.53 microM aorta). Our results support the hypothesis that hypertension and hypercholesterolemia increase vascular sensitivity by increasing Ca2+ permeability. Our results also suggest that hypertension and hypercholesterolemia selectively decrease 5-hydroxytryptamine-induced contractions.     

Percutaneous endoscopic gastrostomy: state of the art, 1998

BDF 9148, a positive cardiac inotrope, relaxes the rat isolated portal vein and the KCl-contracted rat aorta. The aims of our study were to determine the mechanism of action of BDF 9148, and to ascertain whether the relaxing effect of BDF 9148 was maintained in the presence of the hypertrophy associated with hypertension, by investigating the effects of BDF 9148 on the contractility and electrophysiology of aortae of Wistar Kyoto normo-tensive rats (WKY) and Spontaneously Hypertensive Rats (SHRs). High concentrations of veratridine contracted the quiescent rat aorta. BDF 9148 had no effect on the quiescent, but relaxed the KCl-contracted WKY and SHR aorta by a tetrodotoxin insensitive mechanism, and these relaxations decreased with age but were not greatly altered by hypertrophy. The verapamil relaxations of the KCl-contracted aorta were not altered by age or hypertrophy. The ability of KCl to depolarise the aorta was reversed by verapamil, but not by BDF 9148. On the contracted rat aorta, the relaxant responses to acetylcholine were abolished by removal of the endothelium but potentiated by IBMX (10[-6] M), and the responses to isoprenaline were inhibited by propranolol (10[-6] M) but potentiated by forskolin (10[-7] M). The relaxation responses of the KCl-contracted aorta to BDF 9148 were not altered by removal of the endothelium, or by propranolol, forskolin and IBMX. In summary, the effects of verapamil and BDF 9148 on the aorta are different, and thus it is unlikely that the relaxant responses to BDF 9148 on the aorta are due to calcium channel blocking activity. The mechanism of the relaxant effect of BDF 9148 on the aorta remains unknown, but we have shown the response is endothelium-independent, and not mediated by sodium channel opening, hyperpolarization, beta-adrenoceptors, or by stimulating adenylate cyclase or guanylate cyclase.     

Antiatherosclerotic effects of the angiotensin-converting enzyme inhibitors captopril and fosinopril in hypercholesterolemic minipigs

We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the G?ttingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kg/day). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.     

Endothelium-dependent vasodilator effects of the extract from Salviae Miltiorrhizae radix. A study on the identification of lithospermic acid B in the extracts

1. The aqueous extract of Salviae Miltiorrhizae radix (Chinese crude drug named "dan-shen") relaxed the noradrenaline-precontracted aorta with endothelium. 2. Vasodilation by the extract disappeared in aorta without endothelium, and was inhibited by pretreatment with 10(-4) M NG-monomethyl-L-arginine (L-NMMA) or 10(-5) M methylene blue. 3. The inhibition of the extract-induced vasodilation by L-NMMA was reversed by L-arginine (3 x 10(-4) M). 4. The component of the extract was analyzed by chromatography, fast atom bombardment mass spectroscopy (FAB-MS) and 1H-NMR. 5. An active component of the extract, which showed endothelium-dependent vasodilation, was found to be identical with lithospermic acid B.     

Effects of preanesthetic and anesthetic drugs on endothelium-dependent responses in the rat aorta

1. Acetylcholine often fails to induce endothelium-dependent relaxation in human vessels in vitro. Due to the fact that most of these vessels come from surgery, we examined the influence of drugs used in anesthesia on endothelium-dependent responses in rat aorta. 2. Groups of male Wistar rats of the following treatments were utilized: P group, diazepam+promethazine+atropine; I group, pentothal+succinylcholine; IG group, halothane+nitrous oxide; M group, morphine+pancuronium; C group, untreated rats. Dose-response curves to noradrenaline and acetylcholine were determined in rat aorta in vitro, in the presence and absence of endothelium. 3. Acetylcholine induced more relaxation (P < 0.05) in the rat aorta of IG group compared with that of the C group. 4. In the rat aorta from P and IG groups, the contractions produced by several concentrations of noradrenaline were significantly smaller (P < 0.05) when the endothelium was removed. Similar effects occurred in aorta strips of animals previously treated with either atropine, promethazine, cimetidine or halothane. 5. Our results suggest that drugs currently used in anesthesia interfere with some endothelium-dependent effects on isolated rat aorta but according to these results they do not seem to be responsible for the lack of acetylcholine relaxation sometimes described in human vessels in vitro.     

Leukocyte-endothelium interaction during the early stages of hypercholesterolemia in the rabbit: role of P-selectin, ICAM-1, and VCAM-1

The early effects of hypercholesterolemia on leukocyte-endothelium interaction were studied in vivo in the rabbit mesenteric microcirculation. Rabbits fed a 0.5% high-cholesterol (HC) diet showed elevated plasma cholesterol levels during the 1 to 2 weeks of HC feeding (P<0.001 versus control diet-fed rabbits). Intravital microscopy of mesenteric venules revealed that leukocyte rolling had increased 10-fold (P<0.001 versus control-fed group) at the end of the first week of the HC diet, which was sustained after 2 weeks of HC feeding (P<0.001 versus control-fed rabbits). Firm adherence of leukocytes to the endothelium was moderately increased after a 1-week period of hypercholesterolemia (P<0.05) but increased by 12-fold at 2 weeks (P<0.001 versus control diet-fed and P<0.01 versus 1-week HC-fed rabbits). Upregulation of the endothelial cell adhesion molecules P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was observed immunohistochemically on the intestinal microvascular endothelium of HC-fed rabbits. P-selectin was maximally expressed within the first week of the HC diet and remained elevated during the second week of cholesterol feeding (P<0.01 versus control). In contrast, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were moderately upregulated at 1 week but were highly expressed after 2 weeks of the HC diet (P<0.05 and P<0.001 versus control, respectively). Basal release of NO from both mesenteric microvascular and aortic endothelium in cholesterol-fed rabbits was progressively reduced after 1 (P<0.05) and 2 (P<0.01) weeks. Our data suggest that enhanced leukocyte-endothelium interaction occurs in vivo in the rabbit microcirculation during the first 2 weeks of hypercholesterolemia. This phenomenon is associated with impaired basal NO release and progressive endothelial surface expression of endothelial cell adhesion molecules (ie, P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1) in the microvasculature.     

Adherent leukocytes to the aortic wall promotes atherosclerosis in the Watanabe heritable hyperlipidemic rabbits

It is well known that leukocytes adherence to the endothelium of arterial wall occurs in diet-induced hypercholesterolemic animals. We examined the relationship between leukocytes adherence and atherosclerosis in the thoratic aorta of the Watanabe heritable hyperlipidemic rabbits (WHHL rabbits). Five of 2 or 3 months old WHHL rabbits were sacrificed and after perfusion fixation with 2.5% gulutaraldehyde, thoratic aorta was taken out carefully and divided into the 4 portions: Portion 1; cranial side of aortic arch, Portion 2; caudal side of aortic arch, Portion 3; upper side of thoratic aorta except aortic arch, Portion 4; lower side of thoratic aorta except aortic arch. Three to 6 samples from each portion except branching sites were examined using electron microscopy, and the counts of adherent leukocytes (LC) in each portion were calculated. Seven of 6 to 12 months old WHHL rabbits were sacrificed and the internal side of thoratic aorta was cut opened from the ventral side and the atherosclerotic lesions were copied. From these copies, the % area of atherosclerotic plaques (%AT) in each 4 portions as described was calculated using microcomputer. LC in Portion 1 to 4 was 265 +/- 62, 234 +/- 46, 53 +/- 8 and 41 +/- 13/mm2 respectively. LC in Portion 1 or 2 was significantly larger than that in Portion 3 or 4 (p < 0.05). The endothelium to which leukocytes adhered was intact. %AT in Portion 1 to 4 was 68 +/- 8, 63 +/- 8, 40 +/- 8 and 34 +/- 8% respectively. %AT in Portion 1 or 2 was significantly larger than that in Portion 3 or 4 (p < 0.05). It is concluded that leukocytes adherence to the intact endothelium of the arterial wall was one of the geneses and promoters of atherosclerosis in WHHL rabbits.     

Interaction of the allogeneic state and hypercholesterolemia in arterial lesion formation in experimental cardiac allografts

To learn more about the interaction of allogeneic transplantation and hypercholesterolemia in the formation of arterial lesions, we performed heterotopic cardiac transplantation in rabbits. We analyzed lesions in both the coronary arteries and the proximal ascending aorta 6 weeks after surgery in both transplanted and native hearts of normocholesterolemic rabbits and those with diet-induced hypercholesterolemia (serum cholesterol, 1638 +/- 366 mg/dL, n = 6, 6 weeks after transplantation). All animals received cyclosporin A (5 mg.kg-1.d-1) for immunosuppression. The transplanted aortas of hypercholesterolemic animals had thicker intimal lesions than did the native aortas (intima/media ratio, 0.67 +/- 0.4 versus 0.08 +/- 0.1, P < .05) and contained more T cells (37.4 +/- 12.8 versus 5.7 +/- 6.2 per high-power field, P < .001). In normocholesterolemic animals (n = 5) the coronary arteries had negligible lesions in the native heart and only slight and inconsistent intimal lesions in the transplanted heart. In the hypercholesterolemic animals, more coronary arteries had intimal lesions in the transplanted hearts than in the native hearts (74% versus 43%). Coronary artery lesions in the native hearts consisted mostly of foam cells, while those in transplanted hearts had more abundant smooth muscle cells as determined by alpha-actin staining. Intimal endothelial cells in transplanted aortas expressed increased levels of vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 compared with the native vessels subjected to identical levels of cholesterolemia. Medial smooth muscle cells in transplanted aortas contained much higher levels of immunoreactive tumor necrosis factor-alpha than did medial cells of the native aorta in the same hypercholesterolemic animals. The intima of transplanted aortas contained prominent microvessels compared with the native aorta of the hypercholesterolemic rabbits. We conclude that even during treatment with doses of cyclosporine that control acute myocardial rejection, hypercholesterolemia and the allogeneic state act together to augment allograft atherosclerosis, T-cell accumulation, intimal neovascularization, local cytokine expression, and indices of cell activation in arteries.     

Comments on selected recent dysphagia literature

Arterial stiffness may be an indicator of early vascular changes signaling the development of vascular disease, while hypercholesterolemia is a well-recognized promoter of atherogenesis. It has been shown that hypercholesterolemic children have a thicker intima-media in the carotid artery than children with normal cholesterol. The aim of this study was to assess the stiffness of the abdominal aorta in children with hypercholesterolemia. Noninvasive imaging evaluation of the aorta was performed in 85 outpatient children (age, 3 to 14 years) with and without high cholesterol levels ((and) 247 mg/dL [6.4 mmol/L], respectively). Ultrasound imaging of the abdominal aorta that allowed diameter measurements was available in 67 children. Using an image-processing workstation, the maximum and minimum internal diameter of the aorta was measured, and the following indices of elastic properties of the abdominal aorta were derived: arterial strain, pressure-strain elastic modulus, and stiffness. No statistical difference for aortic strain, stiffness, and elastic modulus was found in normocholesterolemic compared with hypercholesterolemic children. The effect of age on the elastic modulus was different in the two groups: in normal children, the elastic modulus increased linearly with age (y = -0.020+0.003 x age [months], P<.001), while the high-cholesterol group had a weak increase in this parameter with age (y = 0.118+0.0009 x age, P = .051). The slope of the regression equations (elastic modulus vage) was significantly different in the two groups (t = 2.45, P = .017). The behavior of arterial stiffness with respect to age was similar, y = 0.677+0.018 x age (P = .002) in normocholesterolemic children and y = 2.06+0.00198 x age (P = .66) in hypercholesterolemic children. The slope of the regression equations (stiffness v. age) was significantly different in the two groups (t = 2.37, P = .021). The present study demonstrates an influence of hypercholesterolemia on age-related modification in the elastic properties of the aorta. A remodeling of the aortic wall in hypercholesterolemic children (cholesterolemia >247 mg/dL) could explain the different age-dependent increase in aortic elastic modulus and stiffness.     

The regional morphological characteristics of the endothelium of the human thoracic aorta in perfusion fixation

The ultramicroscopic organization and the endotheliocyte surface relief in ventral portions of the thoracic part of human aorta and in zones of division of blood flow were studied under conditions of early post mortem examinations and perfusion fixation of corpses of 14 humans dead from accidental causes. Zones of entrance into the intercostal aortas are compared with the straight portions of the aorta and are found to be characterized, as compared with the latters, by polymorphism of the endothelium, higher adhesiveness of its surface to blood elements, as well as by the presence of intravitally de-endothelialized portions localized on the ridge of the intimal valve.     

Effects of adrenomedullin and calcitonin gene-related peptide on contractions of the rat aorta and porcine coronary artery

1. Effects of adrenomedullin and alpha-calcitonin gene-related peptide (CGRP) on the contractions and cytosolic Ca2+ concentrations ([Ca2+]i) of the rat aorta and porcine coronary artery were investigated. Characteristics of the receptors mediating the effects of adrenomedullin and alpha-CGRP were also investigated. 2. Adrenomedullin and alpha-CGRP caused a concentration-dependent relaxation in the rat aorta contracted with noradrenaline. The IC50 values for adrenomedullin and alpha-CGRP were 2.4 nM and 4.0 nM, respectively. The relaxant effects of these peptides were abolished by removal of the endothelium and significantly attenuated by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMMA, 100 microM), but not by a cyclo-oxygenase inhibitor, indomethacin (10 microM). 3. Adrenomedullin and alpha-CGRP increased the endothelial [Ca2+]i in the rat aorta with endothelium, whereas they did not change [Ca2+]i in the smooth muscle. 4. An antagonist of the CGRP1 receptor, CGRP (8-37), antagonized the relaxant effects of alpha-CGRP and the beta-isoform of CGRP (beta-CGRP) but not those of adrenomedullin in the rat aorta. 5. In the porcine coronary artery contracted with U46619, adrenomedullin and alpha-CGRP caused a concentration-dependent relaxation with an IC50 of 27.6 and 4.1 nM, respectively. Removal of the endothelium altered neither the IC50 values nor the maximal relaxations induced by adrenomedullin or alpha-CGRP. When the artery was contracted with high K+ solution (72.7 mM), these peptides caused a small relaxation. 6. Adrenomedullin and alpha-CGRP increased cyclic AMP content and decreased the smooth muscle [Ca2+]i in the porcine coronary artery. 7. CGRP (8-37) significantly antagonized the relaxant effects of adrenomedullin and alpha-CGRP in the porcine coronary artery. However, it had little effect on the relaxations induced by the beta-isoform of CGRP (beta-CGRP). 8. These results suggest that in the rat aorta, adrenomedullin and alpha-CGRP increase the endothelial [Ca2+]i, activate nitric oxide synthase and release nitric oxide, without a direct inhibitory action on smooth muscle. In the porcine coronary artery, in contrast, adrenomedullin and alpha-CGRP directly act on smooth muscle, increase cyclic AMP content, decrease the smooth muscle [Ca2+]i and inhibit contraction. The rat aortic endothelium seems to express the CGRP receptor which is sensitive to alpha-CGRP, beta-CGRP and CGRP (8-37) and the adrenomedullin specific receptor. The porcine coronary smooth muscle, in contrast, seems to express two types of CGRP receptor; one of which is sensitive to alpha-CGRP, CGRP (8-37) and adrenomedullin and the other is sensitive only to beta-CGRP.     

Prevalence of antibodies against virus-like particles of Epidermodysplasia verruciformis-associated HPV8 in patients at risk of skin cancer

The dietary intake of saturated fatty acids affects arteriosclerosis. We studied the effect of supplementation (15% wt/wt) of a hyperlipemic diet (1.3% cholesterol) with evening primrose oil (Oenothera biennis) in four groups of 10 rabbits each. After 6 weeks the aortic endothelium was analyzed morphologically with scanning electron microscopy, and the arterial wall was studied with morphometric techniques and cell nucleus counts. Endothelial functioning was analyzed by measuring prostacyclin synthesis, and thrombogenicity of the subendothelium was studied by perfusion in a Baumgartner annular chamber. Evening primrose oil reduced hypercholesterolemia (from 29 +/- 3 to 12 +/- 2 nmol/l), increased HDL-cholesterol (from 0.5 +/- 0.06 to 0.8 +/- 0.09 nmol/l) and doubled prostacyclin synthesis (from 2.7 +/- 2 to 6.2 +/- 0.7 ng/mg aorta) in rabbits on the hyperlipemic diet, reduced subendothelial surface occupied by platelets (from 6.9 +/- 0.4 to 4.8 +/- 0.3%), and reduced human platelet adhesion on the subendothelium (from 53.3 +/- 6% to 38 +/- 8%, respect to total occupation). Morphological analyses showed that evening primrose oil diminished endothelial lesions caused by the atherogenic diet, reducing area of the arterial wall (from 6.9 +/- 0.2 to 4.7 +/- 0.2 microm2 x 10(6)) and the degree of neointimal proliferation (from 0.6 +/- 0.02 to 0.4 +/- 0.09 microm2 x 10(6)). We conclude that in our experimental model, this dietary supplement enhanced the antithrombotic capacity of the endothelium, reduced subendothelial thrombogenicity, and diminished the extent of vascular wall lesions caused by the hyperlipemic diet.     

Rehabilitation of Guillain-Barré syndrome

In this study, we evaluated the effects of vitamin E on the vascular reactivity and structure of thoracic aorta from streptozotocin (STZ)-diabetic rats. Plasma glucose, cholesterol, and triglyceride concentrations in rats were increased markedly by STZ-diabetes. The thiobarbituric acid (TBA) reactivity level as an index of lipid peroxidation was higher in both plasma and aorta of STZ-diabetic rats compared with controls. The rings of thoracic aorta with or without endothelium were mounted in organ chambers for measurement of isometric tension and were contracted by a single dose (10-5 mol/L) and then cumulative doses of noradrenaline ([NA] 10(-9) to 10(-5) mol/L). Pretreatment with methylene blue (MB) or removal of the endothelium resulted in a similar degree of enhancement in NA-induced contraction of control rings. STZ-diabetes increased the fast and slow components of NA-induced contraction in all experiments. The maximal contractile response of aorta to NA was also augmented by STZ-diabetes, whereas the sensitivity (pD2) remained unaltered. STZ-diabetes resulted in significant increases in the maximum contractile response and sensitivity of aorta to KCl. STZ-diabetic rats showed a significant reduction in the percentage of endothelial response (PER). A group of diabetic rats was treated from the time of diabetes induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned plasma triglycerides toward normal levels. Diabetes-induced abnormal contractility and endothelial dysfunction were significantly but not completely prevented by vitamin E treatment. The endothelium-independent relaxation response to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E treatment. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E treatment can protect the morphological integrity of aorta against STZ-diabetes. The results suggest the following: (1) The increased triglycerides/lipid peroxides may be an important reason for morphological or functional disruption of endothelium and enhanced activation of contractile mechanisms of vascular smooth muscle in STZ-diabetic rats. Both contribute to an increased responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E treatment of STZ-diabetic rats can prevent the development of abnormal contractility and structure and endothelial dysfunction in aorta. (3) The triglyceride- and/or lipid peroxidation-lowering effect of vitamin E may be crucial for the protective effect of this vitamin on the vasculature.     

Evaluation of a new selective medium for the isolation of Corynebacterium urealyticum

1. The objective was to determine whether nitric oxide participates in stress adaptive responses. Acute stress (AS) decreased endothelium-dependent vasoconstriction to noradrenaline (NA) in rat aorta [control rat (CR) 3.90 +/- 0.18, n = 22; AS 2.76 +/- 0.20, n = 13; P < 0.05]. 2. Chronic stress exposure previous to AS (CS) potentiated this effect [CS 1.93 +/- 0.19; n = 9; P < 0.05 related to CR, P < 0.05 related to AS]. 3. Methylene blue and NG-monomethyl-L-arginine, but not indomethacin, restored the decreased aorta reactivity to NA. 4. No reactivity alteration was observed in aorta without endothelium either in both stress conditions or in the presence of inhibitors. These data show that the nitric oxide participates in stress responses.     

Contractility of the rabbit abdominal aorta 4 days after endothelium denudation

The purpose of this study was to evaluate contractility of the rabbit abdominal aorta 4 days after de-endothelialization by balloon catheter. The isometric tension of ring-segments in response to vasoactive agents was monitored. A significant enhancement of contraction to noradrenaline and serotonin was found in aortas 4 days after endothelium denudation as compared with controls with endothelium. The enhancement, however, did not differ from that found already in acutely denuded vessels (immediate denudation). No significant difference in contractility to potassium chloride was found in either group of denuded preparations as compared with controls. The sensitivity to all three vasoactive agents (EC50) was not influenced by denudation. These results indicate that changes in the contractility of denuded vessels are predominantly a consequence of lacking the endothelium as a producer of endothelium-derived relaxing factor. The access of mitogens to the media does not seem to interfere with the magnitude of contraction 4 days after denudation.     

Age-related differences and roles of endothelial nitric oxide and prostanoids in angiotensin II responses of isolated, perfused mesenteric arteries and veins of rats

Dimalonic acid C60 (10(-5) M), a new fullerene derivative, produced an augmentation of phenylephrine-induced tone and reduced both the acetylcholine-induced maximum relaxation and the amplitude of substance P (10(-8) M)-induced relaxation in endothelium-containing thoracic aorta of rabbit; the acetylcholine- and substance P-induced relaxation was restored in the presence of superoxide dismutase (250 U/ml). Dimalonic acid C60 (10(-5) M) did not influence the phenylephrine-induced contractile response in the absence of endothelium, but the acetylcholine-induced relaxation was eliminated by removal of the endothelium. Superoxide anion generation, using hypoxanthine (1 mM)/xanthine oxidase (16 mU/ml), reduced the acetylcholine-induced relaxation and produced an augmentation of phenylephrine-induced tone in endothelium-containing strips; these effects were negated by the addition of superoxide dismutase (250 U/ml). A nitric oxide-generating agent, S-nitroso-N-acetylpenicillamine, caused relaxation of aorta without endothelium in a concentration-dependent manner, and the concentration-response curve was shifted to the right in the presence of dimalonic acid C60. This inhibitory effect of dimalonic acid C60 was also masked in the presence of superoxide dismutase. Sodium nitroprusside-induced relaxation was not affected by either dimalonic acid C60 or superoxide dismutase. These observations suggest that dimalonic acid C60 inhibits endothelium (nitric oxide)-dependent agonist-induced relaxation through the production of superoxide.     

Antiatherogenic effect of estrogen abolished by balloon catheter injury in cholesterol-clamped rabbits

The purpose of this study was to investigate the importance of an intact endothelial cell layer for the direct antiatherogenic effect of estrogen on the arterial wall. Thirty rabbits were bilaterally ovariectomized and subjected to mechanical injury of the endothelium by balloon catheterization of the upper thoracic aorta. Immediately after the operation, treatment was initiated with either 17 beta-estradiol or placebo given intramuscularly. All rabbits were clamped at a similar plasma cholesterol level from 1 week before the operation until the experiment was terminated 13 weeks later. In the undamaged aorta, ie, the aortic arch, the lower thoracic aorta, and the upper abdominal aorta, the estrogen-treated rabbits had one third (P = .06), one sixth (P = .002), and one seventh (P = .001), respectively, the accumulation of cholesterol of the placebo-treated rabbits. In the upper thoracic aorta that had been subjected to mechanical injury of the endothelium, however, aortic cholesterol accumulation was not significantly different between the two groups. Similar results were obtained by histological evaluation of the aortic tissues. Immunohistochemical staining with antibodies against macrophages, smooth muscle cells, and T lymphocytes revealed no significant differences in the intimal distribution of cells between estrogen- and placebo-treated rabbits, except for a higher number of T lymphocytes per unit intimal area of the undamaged aortic arch (P < .0005) in the estrogen-treated-rabbits than the placebo-treated rabbits. This is the first study to demonstrate that the antiatherogenic effect of estrogen is abolished by balloon catheter injury in cholesterol-clamped rabbits. These results may indicate that an intact endothelial cell layer is crucial for the direct antiatherogenic effect of estrogen on the arterial wall.