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H Yoneyama

Publications and source records attributed to H Yoneyama.

At least 19 recordsLinked to original sources
PubMed2001

Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice.

Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically chemoattracts CC chemokine receptor 4-positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhibit the induction of asthmatic reaction in mice elicited by OVA. TARC was constitutively expressed in the lung and was up-regulated in allergic inflammation. The specific Ab against TARC attenuated OVA-induced airway eosinophilia and diminished the degree of airway hyperresponsiveness with a concomitant decrease in Th2 cytokine levels. Our results for the first time indicate that TARC is a pivotal chemokine for the development of Th2-dominated experimental allergen-induced asthma with eosinophilia and AHR. This study also represents the first success in controlling Th2 cytokine production in vivo by targeting a chemokine.

Animals↗
PubMed2001

Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation.

Chemokine-chemokine receptor interaction plays an essential role in leukocyte/dendritic cell (DC) trafficking in inflammation and immune responses. We investigated the pathophysiological roles of secondary lymphoid tissue chemokine (SLC; CCL21) and macrophage inflammatory protein-2 (MIP-2) in the development of acute pulmonary inflammation induced by an intratracheal injection of Propionibacterium acnes in mice. Immunohistochemical studies revealed that SLC was constitutively expressed in the peribronchial areas and perivascular lymphatics in normal mice. MIP-2-positive cells were observed in alveolar spaces in mice challenged with P. acnes. Both neutralization Abs against MIP-2 and CXC chemokine receptor 2 alleviated the P. acnes-induced pulmonary inflammation when injected before P. acnes Ag challenge. On the other hand, polyclonal anti-SLC Abs (pAbs) exacerbated the pulmonary inflammation. The numbers of mature DCs (MHC class II +, CD11c+, and CD86+) as well as macrophages and neutrophils in the P. acnes Ag-challenged lungs were increased, whereas the number of CD4+ T cells, including memory T cells, was decreased. The numbers of mature and proliferating CD4+ T cells (bromodeoxyuridine(+)CD4+) in regional lymph nodes were decreased in mice injected with anti-SLC pAbs compared with those in mice treated with control Abs. An in vitro proliferation assay confirmed the impairment of the Ag-specific T cell response in regional lymph nodes of mice treated with anti-SLC pAbs. These results indicate for the first time a regulatory role for SLC-recruited mature DCs in bridging an acute inflammatory response (innate immunity) and acquired immunity in the lung.

Acute Disease↗
PubMed2001

Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes-induced granulomas in mouse liver. During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associated lymphoid tissue" (PALT). Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Animals↗
PubMed2001

Inhibitory effect of rifampicin on the depressive action of interleukin-1 on cytochrome P-450-linked monooxygenase system.

It has been shown that interleukin 1 (IL-1) depresses cytochrome P-450-linked monooxygenases. In the present study, the effects of rifampicin on the depressive action of IL-1 on the activities and gene expression of xenobiotic metabolizing enzymes in liver microsomes were investigated in vivo using Wistar rats. Among the monooxygenases studied, we especially focused on the induction mechanism for CYP2D, known to be depressed by IL-1 and responsible for the oxidation of xenobiotics, debrisoquine, bufuralol, and sparteine. The CYP2D protein and its messenger RNA (mRNA) were quantitated by Western blot and slot blot hybridization analyses in the groups treated with and without rifampicin and IL-1. The results showed that the depressive action of IL-1 on CYP2D was offset by additional administration of rifampicin, and the P-450 (CYP2D-linked monooxygenase system is up-regulated at the mRNA level by rifampicin. These results show that rifampicin has a blocking effect on the depressive action of IL-1 on the CYP2D subfamily.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2001

L-Arginine improves endothelial function in renal artery of hypertensive Dahl rats.

OBJECTIVES: To clarify whether endothelium-derived contracting factor (EDCF) is developed in renal artery of hypertensive Dahl rats and whether prolonged oral L-arginine treatments prevent development of EDCF and hypertension. DESIGN: The effect of prolonged salt treatment with or without L-arginine on the renal artery was examined. METHODS AND RESULTS: Dahl salt-sensitive and -resistant rats were fed a 0.4 or an 8% NaCl diet for 4 weeks. High sodium intake increased arterial pressure in Dahl salt-sensitive rats. The rings of renal arteries were suspended for isometric tension recording. Only in the hypertensive rats, more than 1 micromol/l acetylcholine induced an endothelium-dependent contraction response. The contraction was completely inhibited by indomethacin or ONO-3708 [prostaglandin H2 (PGH2)/thromboxane A2 (TXA2) receptor antagonist], and partially inhibited by OKY-046 (TXA2 synthetase inhibitor). Acetylcholine-induced relaxation was significantly depressed in hypertensive rats, which was partially improved by SQ29548 (PGH2/TXA2 receptor antagonist). Oral L-arginine, but not ONO-8809 (orally active PGH2/TXA2 receptor antagonist) treatment, inhibited the contraction and amended the relaxation. The endothelium-independent contraction to TXA2 receptor agonist U46619 and relaxation to nitroprusside were not altered by L-arginine treatment The L-Arginine treatment reduced blood pressure and sodium retention with increases in urinary NO2-/NO3- and cGMP excretion. Hydralazine treatment also inhibited development of EDCF. CONCLUSIONS: The present results suggest that impaired endothelium-dependent relaxation to acetylcholine is caused in part by induction of EDCF synthesis/release in renal arteries of hypertensive Dahl rats. L-arginine can attenuate sodium retention and development of hypertension, which lead to a decrease in EDCF synthesis in renal arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

[Clinical analysis of patients with community-acquired pneumonia requiring hospitalization classified by age group].

We classified 1017 patients with community-acquired pneumonia requiring hospitalization experienced in Kawasaki Medical School Kawasaki Hospital during the past 15 years into five age groups (< or = 54 years old, 55-64 years old, 65-74 years old, 75-84 years old, > or = 85 years old). With particular emphasis on the elderly patients, we then compared the clinical and microbiological findings in the five groups. The results were as follows; (1) Half of patients in the over 85 years old group were bed-ridden. (2) The proportion receiving antibiotics before hospitalization decreased with age. (3) There were striking atypical pneumonic symptoms, such as dyspnea and consciousness disturbance in the two age groups over 75 years old. (4) Hypotension (shock) increased with age. (5) Markers of nutritional conditions, such as serum protein, albumin, cholinesterase, and hypoxia remarkably increased in the two age groups over 75 years old. (6) There were no significant differences in the isolation rate of etiological microorganisms. (7) The number of polymicrobial agents in the < or = 54 years old group was lower than that in the other age groups. (8) Mycoplasma pneumoniae was most significantly higher in < or = 54 years old group, Haemophilus influenzae in patients 55-64 years old, and Streptococcus pneumoniae in both 65-74 and 75-84 years old groups. (9) The isolation rate of MSSA, gram-negative bacilli such as Klebsiella pneumoniae, Pseudomonas aeruginosa, respiratory viruses increased with age. (10) The amount of sepsis increased with age. (11) The prognosis was poor in the two groups over 75 years old because the mortality rate (over 10%) was higher that for the other age groups.

Age Distribution↗
PubMed2001

[Clinical analysis of patients with community-acquired pneumonia caused by a mixed infection of polymicrobial agents--including a comparative study of an infectious group with monomicrobial agents and an infectious group with unknown agents].

We clinically analyzed 83 patients with community-acquired pneumonia caused by a mixed infection of polymicrobial agents who we have treated during the past 15 years. A comparative study among three groups; an infectious group with polymicrobial agents (83 cases), an infectious group with monomicrobial agents (335 cases), and an infectious group with unknown agents (599 cases) was performed. The results were as follows; (1) The highest percentage of patients were elderly and bedridden. (2) Striking atypical pneumonic symptoms, including dyspnea, consciousness disturbance, gastrointestinal symptoms and hypotension (shock) were present. (3) Laboratory findings of poor nutritional conditions, including decreases in serum protein, albumin, and cholineesterase, and hypoxia remarkably increased. (4) The prognosis was poor because the mortality rate (15.7%) was higher. (5) There were two polymicrobial agents for 75 patients and three agents for 8 patients. The coupling of polymicrobial agents was most frequent in five patients with Haemophilus influenzae + MSSA and five with H. influenzae + respiratory virus. These results suggest that the patients with community-acquired pneumonia caused by a mixed infection of polymicrobial agents had clinical features and causative microorganisms resembling those of elderly patients with community-acquired pneumonia. We recommended that treatment with antibiotics for them was adequate if the treatment resemble that of elderly patients.

Adolescent↗
PubMed2001

[Comparison of community-acquired pneumonia in relation to influenza A and RS virus infections].

We experienced 142 cases with community-acquired pneumonia between April 1998 and March 2000. By measuring the titers of respiratory viruses for these cases, we were able to identify acute phase infections of influenza A virus in 10 cases and RS virus in 6 cases and determined that there was an increase in community-acquired pneumonia during both winter seasons. Thereafter we compared the clinical features of community-acquired pneumonia with regard to these two types of virus infection by dividing the patients into two groups, both of which frequently included in the elderly. In the influenza virus group, such general symptoms as high fever, headache and general fatigue were dominant. Common bacteria were isolated in nine cases with mixed infection; four of them with Streptococcus pneumoniae. In the RS virus group, there were fewer general symptoms and common bacteria were isolated in four cases with mixed infection; three with Haemophilus influenzae. The severity of the illness was greater in the Influenza virus group; i.e.) three cases required mechanical ventilation and two of these three cases died. In the RS virus group, on the other hand, the prognosis was good because no mechanical ventilation was required and there were no deaths. Influenza vaccination is especially important for the elderly, because the epidemiology of the influenza virus groups showed none had a history of influenza vaccination in this study.

Adult↗
PubMed2001

Effect of isosorbide dinitrate on nitric oxide synthase under hypoxia.

Nitric oxide synthase (NOS) catalyzes nitric oxide (NO) formation from L-arginine in the presence of molecular oxygen and NADPH. NO is involved in the regulation of microvasculature. Isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN) have been widely used as vasodilators to treat acute myocardial ischemia, their biological effects being due to the release of NO. In this investigation, the effects of ISDN and GTN on NOS activity in the presence or absence of oxyhemoglobin under hypoxia and normoxia were studied. The apparent K(m) values for molecular oxygen were 21.6 +/- 1.5 and 9.4 +/- 1.3 micromol/l for nNOS and eNOS, respectively. ISDN liberated NO in a concentration- and pH-dependent manner, but no differences between hypoxia and normoxia were observed. The NO release from ISDN was also measured directly by an electron spin resonance spectral method with N-(dithiocarboxy)sarcosine-Fe complex as a NO-trapping agent. ISDN increased nNOS and eNOS activities in the presence of 30 micromol/l oxyhemoglobin under hypoxia, while it did not affect nNOS and eNOS activities under normoxia. In the absence of oxyhemoglobin, ISDN inhibited nNOS and eNOS activities under both hypoxic and normoxic experimental conditions. The rate of oxygen release from oxyhemoglobin under hypoxia was increased 3 times in the presence of 1 mmol/l ISDN. In contrast to ISDN, GTN could not release NO spontaneously, and it also did not affect nNOS and eNOS activities in the absence or presence of 30 micromol/l oxyhemoglobin under both hypoxic and normoxic conditions. These results indicated that the NO release from ISDN is different from that of GTN, and the increase of NOS activity by ISDN in the presence of oxyhemoglobin under hypoxia is ascribed to the increase in molecular oxygen concentration.

Animals↗
PubMed2000

Localization of the outer membrane subunit OprM of resistance-nodulation-cell division family multicomponent efflux pump in Pseudomonas aeruginosa.

The outer membrane subunit OprM of the multicomponent efflux pump of Pseudomonas aeruginosa has been assumed to form a transmembrane xenobiotic exit channel across the outer membrane. We challenged this hypothesis to clarify the underlying ambiguity by manipulating the amino-terminal signal sequence of the OprM protein of the MexAB-OprM efflux pump in P. aeruginosa. [(3)H]Palmitate uptake experiments revealed that OprM is a lipoprotein. The following lines of evidence unequivocally established that the OprM protein functioned at the periplasmic space. (i) The OprM protein, in which a signal sequence including Cys-18 was replaced with that of periplasmic azurin, appeared in the periplasmic space but not in the outer membrane fraction, and the protein fully functioned as the pump subunit. (ii) The hybrid OprM containing the N-terminal transmembrane segment of the inner membrane protein, MexF, appeared exclusively in the inner membrane fraction. The hybrid protein containing 186 or 331 amino acid residues of MexF was fully active for the antibiotic extrusion, but a 42-residue protein was totally inactive. (iii) The mutant OprM, in which the N-terminal cysteine residue was replaced with another amino acid, appeared unmodified with fatty acid and was fractionated in both the periplasmic space and the inner membrane fraction but not in the outer membrane fraction. The Cys-18-modified OprM functioned for the antibiotic extrusion indistinguishably from that in the wild-type strain. We concluded, based on these results, that the OprM protein was anchored in the outer membrane via fatty acid(s) attached to the N-terminal cysteine residue and that the entire polypeptide moiety was exposed to the periplasmic space.

Azurin↗
PubMed2000

Impairment of lymphopoiesis and myelopoiesis in mice reconstituted with bone marrow-hematopoietic progenitor cells expressing SDF-1-intrakine.

Both SDF-1 and CXCR4 disruption are lethal to mice at the embryonic stage and cause abnormalities in B lymphopoiesis, myelopoiesis, cardiogenesis, vasculogenesis, and cerebellar development. To investigate the role of SDF-1 and CXCR4 in hematopoiesis during the adult stage, mice reconstituted with bone marrow-derived hematopoietic progenitor cells transduced with either the SDF-1 or a genetically modified SDF-1-intrakine gene using a retroviral expression vector were analyzed. Flow cytometric (FCM) analysis showed a dramatic reduction of CXCR4 expression on the cells of intrakine-transduced mice, whereas CCR7 and CCR1 expression was unchanged or marginally decreased on splenocytes. Migration of splenocytes and bone marrow cells to SDF-1 was markedly suppressed in intrakine-transduced mice. FCM analysis of bone marrow cells of intrakine-transduced mice exhibited decreased numbers of pro-B (B220(+) CD43(+)), pre-B (B220(+) CD43(-)), and immature B (B220(+) IgM(+)) cells and a decreased number of granulocytes/myeloid (Gr1(+) CD11b(+)) cells. Impaired B lymphopoiesis and myelopoiesis in intrakine-transduced mice were confirmed by an in vitro colony-forming assay of bone marrow cells. In contrast, B lymphopoiesis and myelopoiesis were enhanced in SDF-1-transduced mice. Interestingly, T-cell maturation in the thymus was impaired both in intrakine- and SDF-1-transduced mice, suggesting that SDF-1 and CXCR4 play an important role in T lymphopoiesis as well as in B lymphopoiesis and myelopoiesis in adults. These results demonstrate an essential role of CXCR4 and its ligand SDF-1 in adult hematopoiesis, and they indicate the intrakine method as a powerful tool for functional analysis of chemokines/chemokine receptors in vivo and as a potential therapeutic approach for acquired immunodeficiency syndrome.

Animals↗
PubMed2000

Function of the membrane fusion protein, MexA, of the MexA, B-OprM efflux pump in Pseudomonas aeruginosa without an anchoring membrane.

Resistance of Pseudomonas aeruginosa to multiple species of antibiotics is largely attributable to expression of the MexA, B-OprM efflux pump. The MexA protein is thought to be located at the inner membrane and has been assumed to link the xenobiotics-exporting subunit, MexB, and the outer membrane channel protein, OprM. To verify this assumption, we analyzed membrane anchoring and localization of the MexA protein. n-[9, 10-(3)H]Palmitic acid incorporation experiments revealed that MexA was radiolabeled with palmitic acid, suggesting that the MexA anchors the inner membrane via the fatty acid moiety. To evaluate the role of lipid modification and inner membrane anchoring, we substituted cysteine 24 with phenylalanine or tyrosine and tested whether or not these mutant MexAs function properly. When the mutant mexAs were expressed in the strain lacking chromosomal mexA in the presence of n-[9,10-(3)H]palmitic acid, we found undetectable radiolabeling at the MexA band. These transformants restored antibiotic resistance to the level of the wild-type strain, indicating that lipid modification is not essential for MexA function. These mutant strains contained both processed and unprocessed forms of the MexA proteins. Cellular fractionation experiments revealed that an unprocessed form of MexA anchored the inner membrane probably via an uncleaved signal sequence, whereas the processed form was undetectable in the membrane fraction. To assure that the lipid-free MexA polypeptide could be unbound to the membrane, we analyzed the two-dimensional membrane topology by the gene fusion technique. A total of 78 mexA-blaM fusions covering the entire MexA polypeptide were constructed, and all fusion sites were shown to be located at the periplasm. To answer the question of whether or not membrane anchoring is essential for the MexA function, we replaced the signal sequence of the MexA protein with that of the azurin protein, which contains a cleavable signal sequence but no lipid modification site. The signal sequence of the azurin-MexA hybrid protein was properly processed and bore the mature MexA, which was fully recovered in the soluble fraction. The transformant, which expressed azurin-MexA hybrid protein restored the antibiotic resistance to a level indistinguishable from that of the wild-type strain. We concluded from these results that the MexA protein is fully functional as expressed in the periplasmic space without anchoring the inner membrane. This finding questioned the assumption that the membrane fusion proteins connect the inner and outer membranes.

Amino Acid Sequence↗
PubMed2000

TNF-alpha is a potent inducer for IFN-inducible protein-10 in hepatocytes and unaffected by GM-CSF in vivo, in contrast to IL-1beta and IFN-gamma.

We have recently shown that IFN-inducible protein 10 (IP-10), a member of the CXC chemokine family, is induced in hepatocytes surrounded by infiltrative mononuclear cells in human livers with chronic hepatitis. Hence, we examined the kinds of stimuli that can induce IP-10 expression in hepatocytes in vivo. While the liver expressed three chemokine genes (IP-10, JE/MCP-1, KC/GRO) in a tissue-specific fashion following systemic treatment with pro-inflammatory cytokines, IP-10 mRNA expression showed the most marked liver-specificity. Pretreatment with GM-CSF selectively inhibited IL-1beta, but not TNF-alpha-induced IP-10 mRNA expression. In situ hybridization analysis in the liver and Northern hybridization analysis in isolated liver cell fractions from rodents treated with pro-inflammatory cytokines revealed cellular sources of chemokine expression. IP-10 mRNA expression in hepatocytes was induced by i.v. administration of TNF-alpha, and to a much lesser extent in response to IL-1beta and IFN-gamma, whereas Kupffer cells and endothelial cells expressed IP-10 mRNA equivalently in response to these three stimuli. On the other hand, JE/MCP-1 mRNA expression was detected only in non-parenchymal cells in response to TNF-alpha and IL-1beta, but not in response to IFN-gamma. KC/GRO mRNA expression was also induced mainly in sinusoidal cells by treatment with TNF-alpha or IL-1beta, although it was detected to a lesser extent in hepatocytes. Our results demonstrated that chemokine induction is stimulus-, tissue- and cell type-specific and that IP-10 (but not MCP-1) is inducible in hepatocytes by TNF-alpha most potently, even in the presence of GM-CSF, suggesting the specific role of TNF-alpha-induced IP-10 on intralobular mononuclear infiltration in chronic hepatitis.

Animals↗
PubMed2000

Potassium augments vascular relaxation mediated by nitric oxide in the carotid arteries of hypertensive Dahl rats.

The present study was designed to determine whether and how potassium supplementation improves the endothelial function of carotid arteries of hypertensive Dahl rats. Dahl salt-sensitive rats were fed a high sodium diet, a high sodium plus potassium-supplemented diet, a normal rat chow, or a potassium-supplemented diet for 4 weeks. High sodium intake significantly increased the blood pressure, which was attenuated by potassium supplementation. The isometric tension of rat-isolated carotid rings was measured. In norepinephrine-precontracted rings, the relaxation in response to acetylcholine, adenosine 5'-diphosphate (ADP), and isoproterenol were significantly attenuated in hypertensive Dahl rats, which was improved by potassium supplementation. Pretreatment with N(G)-nitro-L-arginine methyl ester blocked the responses to acetylcholine and ADP, and eliminated the difference in relaxation in response to isoproterenol. The endothelium-independent relaxation in response to forskolin, S-nitroso-N-acetyl-DL-penicillamine, and sodium nitroprusside was significantly attenuated in hypertensive Dahl rats, which was not affected by potassium supplementation. The results indicated that salt-induced hypertension was associated with marked alterations in the endothelial and vascular smooth muscle functions of the carotid arteries of Dahl rats. Potassium supplementation ameliorated the endothelial but not the smooth muscle function. The protective effect of potassium appeared to be achieved through increased endothelial nitric oxide production. The current studies, in conjunction with our recent studies on nitric oxide synthase activity in the kidney, strongly suggest that potassium attenuates development of hypertension by increasing nitric oxide production in Dahl rats.

Acetylcholine↗
PubMed2000

A Th2 chemokine, TARC, produced by keratinocytes may recruit CLA+CCR4+ lymphocytes into lesional atopic dermatitis skin.

Atopic dermatitis is an inflammatory skin disease in which the inflammation is characterized by the influx of lymphocytes into the dermis. It is generally believed that atopic dermatitis is a Th2-type disease, i.e., the T lymphocytes produce interleukin-4, interleukin-5, interleukin-10, and interleukin-13, although it has become evident in recent years that the cytokine profile in the skin changes during the course of the disease towards a Th1-Th2 mixed cytokine profile (interferon-gamma, tumor necrosis factor alpha, and interleukin-2). The lymphocytes that home into the skin express cutaneous lymphocyte-associated antigen, and it has recently been shown that most of the lymphocytes in this population express the chemokine receptor CCR4. CCR4 is the receptor for the CC chemokine TARC (thymus and activation regulated chemokine), and this chemokine is expressed predominantly by keratinocytes in the basal layer of the epidermis of lesional atopic dermatitis skin in mice. In humans, however, it was shown to be expressed in the endothelial cells of the dermis. We have examined the peripheral blood mononuclear cells of atopic dermatitis patients for the expression of cutaneous lymphocyte-associated antigen and CCR4 and compared them with peripheral blood mononuclear cells from normal controls. We found that the proportion of CLA+CCR4+ lymphocytes is upregulated in atopic dermatitis patients. In addition we have examined skin biopsies of lesional and non-lesional skin from atopic dermatitis patients and found that the keratinocytes, but not the endothelial cells, produce TARC in the lesional but not in the nonlesional skin. To gain insight in the stimulatory mechanisms for TARC production in keratinocytes, as previously observed in mice, we cultured HaCaT cells and found that interferon-gamma and tumor necrosis factor alpha work synergistically to induce TARC production. These observations suggest that the induction of TARC production in keratinocytes plays an important role in the late phase skin invasion by CCR4+CLA+ Th2-type lymphocytes in atopic dermatitis.

Animals↗
PubMed2000

Acute production of vascular superoxide by angiotensin II but not by catecholamines.

OBJECTIVE: To determine whether vascular superoxide is rapidly released by angiotensin II and is involved in vascular contraction. DESIGN: The effect of superoxide dismutase (SOD) on angiotensin II induced elevation of mean arterial blood pressure was measured. Subsequently, acute production of vascular superoxide by angiotensin II and its effect on isometric tension were measured in rat aortic rings. The effects of catecholamines were concomitantly measured. METHODS AND RESULTS: The acute pressor effects of angiotensin II were significantly reduced when rats were pretreated intravenously with SOD. When angiotensin II was added on aortic segments in the presence of Cypridina luciferin analog, immediate elevations of chemiluminescence were observed which were inhibited by SOD. Furthermore, angiotensin II-induced elevations of isometric tension in aortic rings were significantly reduced by SOD. The effects of epinephrine and norepinephrine were concomitantly measured and were not significant CONCLUSIONS: The acute superoxide producing effect is likely to be specific to angiotensin II, because such a significant modification of the effects was not observed for catecholamines. Our results suggest that angiotensin II causes acute vascular superoxide production, which may be involved in the acute pressor effects.

Angiotensin II↗