Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin converting enzyme (ACE) is present on endothelial cells and plays a role in regulating blood pressure in vivo by converting angiotensin I to angiotensin II and metabolizing bradykinin. Since ACE activity is decreased in vivo in sepsis, the ability of lipopolysaccharide (LPS) to suppress endothelial cell ACE activity was tested by culturing human umbilical vein endothelial cells (HUVEC) for 0-72 hr with or without LPS and then measuring ACE activity. ACE activity in intact HUVEC monolayers incubated with LPS (10 micrograms/ml) decreased markedly with time and was inhibited by 33%, 71%, and 76% after 24 hr, 48 hr, and 72 hr, respectively, when compared with control, untreated cells. The inhibitory effect of LPS was partially reversible upon removal of the LPS and further incubation in the absence of LPS. The LPS-induced decrease in ACE activity was dependent on the concentrations of LPS (IC50 = 15 ng/ml at 24 hr) and was detectable at LPS concentrations as low as 1 ng/ml. That LPS decreased the Vmax of ACE in the absence of cytotoxicity and without a change in Km suggests that LPS decreased the amount of ACE present on the HUVEC cell membrane. While some LPS serotypes (Escherichia coli 0111:B4 and 055:B5, S. minnesota) were more potent inhibitors of ACE activity than others (E. coli 026:B6 and S. marcescens), all LPS serotypes tested were inhibitory. These finding suggest that LPS decreases endothelial ACE activity in septic patients; in turn, this decrease in ACE activity may decrease angiotensin II production and bradykinin catabolism and thus play a role in the pathogenesis of septic shock.
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PMID:Lipopolysaccharides decrease angiotensin converting enzyme activity expressed by cultured human endothelial cells. 131 Mar 27

Acute pulmonary oedema can be induced by intraperitoneal injection of Escherichia coli endotoxin in the mouse. A fall in serum angiotensin converting enzyme activity is found in mice given endotoxin and in patients with septic adult respiratory distress syndrome, and has been proposed as an indicator of lung microvascular injury. Protein concentration and angiotensin converting enzyme activity in serum, lung, and bronchoalveolar lavage fluid were determined in male mice up to eight hours after injection of endotoxin. By six hours the serum protein concentration had increased and the bronchoalveolar lavage fluid protein concentration had fallen, suggesting fluid shift into the lung. Angiotensin converting enzyme activity fell in serum and lung but increased in bronchoalveolar lavage fluid. As these changes in enzyme activity were not paralleled by changes in protein concentration they are unlikely to be a result of fluid shift or protein leak, and may indicate an active role of the enzyme in the response to sepsis.
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PMID:Angiotensin converting enzyme and endotoxin induced lung damage in the mouse. 299 46

Angiotensin converting enzyme (ACE) is present in the endothelial cells of the normal lung where it converts angiotensin I to angiotensin II and inactivates bradykinin. It has been suggested that during endothelial injury ACE is sloughed into the blood, and that if the alveolar capillary membrane is injured, also into the alveolar lining fluid. Seven patients with adult respiratory distress syndrome (ARDS), were compared to 11 normal control subjects, nine patients with sarcoidosis, and six with idiopathic pulmonary fibrosis. Total, differential cell counts and ACE determinations were performed on bronchoalveolar lavage fluid in the ARDS group. ACE was detectable in the BAL of all but one ARDS patient. It was concluded that BAL ACE is elevated in some ARDS patients, especially those with infectious causes of lung injury. Increased ACE may reflect endothelial damage or local increase in ACE production in response to sepsis.
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PMID:Angiotensin converting enzyme in bronchoalveolar lavage in ARDS. 302 28

The present study evaluated the pathogenetic roles of three kinds of regulatory peptide. The results showed that (i) plasma endothelin (ET) level elevated significantly in septic shock rats, persistent intravenous drip of low doses ET caused development of shock state in normal rats and the irreversible outcome of light hemorrhagic shock. Furthermore, i. v. administration of specific ET-antiserum was significantly effective to septic shock rats. (ii) Plasma calcitonin gene-related peptide (CGRP) increased by 260% in septic shock rats, i. v. drip of low doses CGRP both in early and late sepsis were effective to shock rats. (iii) Angiotensin-II (ANG-II) contents of heart and aorta increased dramatically both in early and late septic shock, and inhibiting its increase with Captopril in late sepsis significantly improved the shock state, but results were inverse in early sepsis. It could be concluded that ET was one of the most important factors participating in the pathogenesis of shock, CGRP had a compensatory regulatory role in shock and the role of tissue ANG-II was different during different periods of shock.
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PMID:Role of regulatory peptide in pathogenesis of shock. 806 88

Peroxynitrite is a potent oxidant formed endogenously by the near diffusion-limited reaction of nitric oxide with superoxide anion. Peroxynitrite specifically adds a nitro group to the ortho position of the phenolic ring of free and protein-associated tyrosines to form the stable product 3-nitro-L-tyrosine. Systemic administration of 3-nitro-L-tyrosine markedly inhibits the subsequent hemodynamic responses to alpha 1- and beta-adrenoceptor agonists in anesthetized rats. Angiotensin II is an important modulator of vascular tone. The vasoconstrictor effects of this hormone are known to involve the release of catecholamines from sympathetic tissues. In the present study, we examined whether 3-nitro-L-tyrosine (2.5 mumol/kg i.v.) would attenuate the hemodynamic responses produced by angiotensin II (0.1-1.0 microgram/kg i.v.). Angiotensin II produced increases in mean arterial pressure, and renal and mesenteric vascular resistances, but no changes in hindquarter vascular resistance. The pressor and renal and mesenteric vasoconstrictor responses produced by angiotensin II were significantly attenuated 30-60 min following the administration of 3-nitro-L-tyrosine. Further attenuation of these responses was evident 120-180 min following the administration of 3-nitro-L-tyrosine. The alpha 1-adrenoceptor antagonist prazosin also diminished the pressor and renal and mesenteric vasoconstrictor responses produced by angiotensin II. These results demonstrate that 3-nitro-L-tyrosine inhibits the hemodynamic responses to angiotensin II, possibly through the inhibition of alpha 1-adrenoceptor-mediated events. The effect of 3-nitro-L-tyrosine on the hemodynamic action of angiotensin II raises the possibility that 3-nitro-L-tyrosine may be involved in the pathogenesis of the hemodynamic disturbances associated with inflammatory conditions, such as atherosclerosis, ischemia-reperfusion, and sepsis, where formation of peroxynitrite is favored.
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PMID:The peroxynitrite product 3-nitro-L-tyrosine attenuates the hemodynamic responses to angiotensin II in vivo. 896 Aug 80

Septic shock is characterized by hypotension and decreased systemic vascular resistance and impaired vascular reactivity. Renal vasoconstriction markedly contrasts with sepsis-induced generalized systemic vasodilation, which is strongly dependent on nitric oxide. Whether maintained renal vascular reactivity to vasoconstrictors contributes to the decrease in renal blood flow (RBF) and GFR observed during LPS-induced sepsis was tested by assessment of the acute effects of pressor agents on mean arterial pressure (MAP) and renal hemodynamics in endotoxemic and control mice. LPS-injected mice displayed lower MAP, RBF, and GFR than controls (P < 0.001). Despite a lower MAP, basal renal vascular resistance (RVR) was higher during endotoxemia (P < 0.02). Angiotensin II infusion produced a weaker MAP response in septic mice (24 versus 37%; P < 0.005), suggesting impaired vasoconstriction and hyporeactivity. A similar MAP increase was observed between groups during norepinephrine (NE) infusion. The MAP increase to nitric oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME) was much greater in LPS-treated mice (41 versus 15%, P = 0.01), indicating a strong influence of nitric oxide in sepsis. In contrast, the RBF and RVR responses to angiotensin II, NE, or L-NAME were similar in both groups. Moreover, vasopressin produced greater changes in MAP, RBF, and RVR in septic mice than in controls. Among the vasoconstrictor challenges, only NE ameliorated the decrease in GFR 14 h after LPS injection. The in vivo results demonstrate that the renal microvasculature displays a normal or enhanced reactivity to constrictor agents as compared with nonrenal circulatory beds. Such responsiveness may contribute to reduced RBF and GFR during endotoxemia.
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PMID:Maintenance of renal vascular reactivity contributes to acute renal failure during endotoxemic shock. 1556 66

HIV-infected patients may present with a variety of patterns of renal involvement. Acute renal failure is common and most often a result of sepsis, hypotension and nephrotoxic agents. It is potentially avoidable, and support through the period of renal failure may lead to resolution of the renal dysfunction. HIV-associated nephropathy is a unique pattern of sclerosing glomerulopathy that ranges in prevalence form 1 to 10 per cent of the HIV infected population in different geographic locales. This complication of HIV infection will likely present a growing challenge to the medical community as HIV infection continues to spread worldwide. Deciphering the pathogenitic mechanisms of this most rapidly progressive form of focal segmental glomerulosclerosis is not only clinically relevant, but will hopefully provide valuable insights into the medication of the more common idiopathic form of the disease. The potential for improved renal survival of patients with HIV-associated nephropathy ahs become more realistic with the development and the use of antiretroviral agents, as well as studies on the role of immunosuppression and Angiotensin Converting Enzyme (ACE) inhibition in this population.
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PMID:The Kidney: An important target for HIV infection. 1758 Sep 96

Altered expression of endothelial markers - especially adhesion molecules - is diagnostically helpful for diagnosis of ante mortal undiagnosed sepsis. Up to now it is unclear whether (1) expression of Angiotensin converting enzyme (ACE) and/or VE-cadherin (VEC) plays a comparable role, (2) whether expression intensity correlates with post mortem interval. Fifty-nine lung specimens (20 lung specimens with regular morphology from tumour lobectomies, 39 from patients who died of septic ARDS due to microbiologically proven Gram-negative sepsis) were stained with an antibody against ACE (1:80) resp. VEC (1:100). All specimens showed vessel type specific expression patterns for ACE and VEC which was dramatically reduced in sepsis. ACE staining intensity did not correlate with time between death and autopsy. VEC staining was slightly but statistically not significantly reduced with increasing time interval. Pulmonary VEC and ACE expression are reduced in septic ARDS. However, as neither ACE nor VEC expression correlates with time interval between death and post mortem, expression intensities of VEC or ACE are no reliable indices for time elapsed since death.
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PMID:VE-cadherin and ACE: markers for sepsis in post mortem examination? 1840 93

The morphological and functional integrity of the microcirculation is compromised in many cardiovascular diseases such as hypertension, diabetes, stroke, and sepsis. Angiotensin converting enzyme inhibitors (ACEi), which are known to favor bradykinin (BK) bioactivity by reducing its metabolism, may have a positive impact on preventing the microvascular structural rarefaction that occurs in these diseases. Our study was designed to test the hypothesis that BK, via B2 receptors (B2R), protects the viability of the microvascular endothelium exposed to the necrotic and apoptotic cell death inducers H(2)O(2) and LPS independently of hemodynamics. Expression (RT-PCR and radioligand binding) and functional (calcium mobilization with fura-2AM, and p42/p44MAPK and Akt phosphorylation assays) experiments revealed the presence of functional B2R in pig cerebral microvascular endothelial cells (pCMVEC). In vitro results showed that the cytocidal effects of H(2)O(2) and LPS on pCMVEC were significantly decreased by a BK pretreatment (MTT and crystal violet tests, annexin-V staining/FACS analysis), which was countered by the B2R antagonist HOE 140. BK treatment coincided with enhanced expression of the cytoprotective proteins COX-2, Bcl-2, and (Cu/Zn)SOD. Ex vivo assays on rat brain explants showed that BK impeded (by approximately 40%) H(2)O(2)-induced microvascular degeneration (lectin-FITC staining). The present study proposes a novel role for BK in microvascular endothelial protection, which may be pertinent to the complex mechanism of action of ACEi explaining their long-term beneficial effects in maintaining vascular integrity.
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PMID:Bradykinin protects against brain microvascular endothelial cell death induced by pathophysiological stimuli. 1978 24

Acute renal failure occurs in intensive care units as part of multiple organ injuries as well as in connection with sepsis and other severe diseases. The corresponding mortality rate remains high. High age and blood pressure, vascular diseases and diabetes are its risk factors. Angiotensin convertase inhibitors and angiotensin receptor blockers cause a functional "nephrectomy", especially when combined with anti-inflammatory drugs in situations of fluid deficit. Acute ischemic tubular necrosis is the most common cause. Treatment involves usually correction of hemodynamic abnormalities, fluid and other supportive therapy, elimination of obstructions, and dialysis.
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PMID:[Acute renal failure]. 2152 20


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