UMLS:C0432222 - FACTA Search

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Query: UMLS:C0432222 (SEM)
47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated mechanisms by which hypoxia produces relaxation of the aorta and tested the hypothesis that these mechanisms are altered during chronic hypertension. Tension of thoracic aortae from normotensive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) was measured in an organ bath under control conditions and at two levels of hypoxia. In WKY rats, mild and severe hypoxia produced relaxation of the aortae (precontracted with phenylephrine) by 33 +/- 4% and 82 +/- 3%, respectively (mean +/- SEM). Removal of endothelium or administration of NG-nitro-L-arginine (10(-4) mol/L), an inhibitor of nitric oxide synthase, abolished relaxation of the aortae in response to mild hypoxia but did not affect relaxation during severe hypoxia. Glibenclamide (10(-6) mol/L), an inhibitor of potassium channels, attenuated relaxation of the aortae during mild and severe hypoxia by 49 +/- 16% and 74 +/- 4%, respectively. In SHRSP, mild hypoxia produced little relaxation of the aortae (3 +/- 4%, P < .05 compared with WKY). Indomethacin did not increase relaxation to mild hypoxia in SHRSP, which suggests that a cyclooxygenase-derived contracting factor does not contribute to impaired relaxation. Severe hypoxia relaxed the aortae by 86 +/- 4% in SHRSP, and glibenclamide inhibited this response by 60 +/- 9%. These findings suggest that relaxation of the aorta in response to mild hypoxia in WKY rats is mediated primarily by endothelium-derived relaxing factor, and the response to mild hypoxia is markedly impaired in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relaxation of the aorta during hypoxia is impaired in chronically hypertensive rats. 753 13

Native LDL and LDL oxidized under various conditions were compared in terms of their ability to activate platelets. Native LDL did not induce platelet shape change or aggregation, even at high concentrations (2 mg protein/mL). LDL was mildly oxidized with either CuSO4 (mox-LDL) or 3-(N-morpholino)sydnonimine (SIN-1-LDL). Analysis of mox-LDL and SIN-1-LDL showed a small increase of dienes (E234nm from 0.28 +/- 0.04 to 0.55 +/- 0.09, mean +/- SD) and thiobarbituric acid-reactive substance (from 0 to 10.6 +/- 1.5 nmol/mg, mean +/- SEM), no change in apo B electrophoretic mobility, and a minor (12% to 30%) decrease in polyunsaturated fatty acid content. Interestingly, this small oxidative modification of LDL dramatically changed its effect on platelets. Irreversible aggregation and secretion were induced by a threshold concentration of 0.4 mg protein/mL. In contrast, LDL thoroughly oxidized with CuSO4 (ox-LDL) did not aggregate platelets. Although mox-LDL was depleted in antioxidants (alpha- and gamma-tocopherol, alpha- and beta-carotene, and other carotenoids), incubation of mox-LDL with exogenous alpha-tocopherol did not reverse its ability to induce platelet aggregation and secretion. Preincubation of platelets with the cyclooxygenase inhibitor aspirin or the phospholipase A2 inhibitors trifluoperazine, quinacrine, 4-bromophenacyl bromide, and propranolol completely prevented platelet aggregation and secretion caused by mox-LDL or SIN-1-LDL. These results indicate that mildly oxidized LDL activates platelets through a phospholipase A2/cyclooxygenase-dependent pathway. The complete inhibition of mox-LDL-induced platelet aggregation by aspirin could contribute to its beneficial effect in cardiovascular disease.
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PMID:Mildly oxidized LDL induces platelet aggregation through activation of phospholipase A2. 762 6

We compared the effects of urodilatin (URO) and atrial natriuretic factor (ANF) in normal and hydronephrotic kidneys (HNK) of rats. Furthermore, the impact of blocking different vasoactive hormones on the action of natriuretic peptides on vessels of cortical (C) and juxtamedullary (JM) glomeruli was studied in HNK by using URO. In normal kidneys, effects of URO and ANF (1.2, 2.4, 4.8, 12, and 19.10(-11) mol.kg-1.min-1 i.v.) were not significantly different. At 12.10(-11) mol.kg-1.min-1, URO and ANF increased urine flow 5.4 +/- 1.7 and 3.0 +/- 0.8-fold, increased urinary sodium excretion 20.7 +/- 8.8 and 10.3 +/- 4.0-fold, and decreased blood pressure by 13 +/- 2% and 12 +/- 1%, respectively (mean +/- SEM). In HNK, URO and ANF (0.4, 0.9, and 2.0.10(-11) mol.kg-1.min-1 i.v. and local application of 0.5, 1.0, and 2.0.10(-9) M) dose-dependent dilated preglomerular vessels (max approximately 20%), constricted efferent arterioles (max approximately 15%), and increased glomerular blood flow of C glomeruli in an identical fashion. Comparing URO effects on C and JM arterioles (0.4 and 0.9.10(-11) mol.kg-1.min-1 i.v.), JM responses were about one third of C responses. Angiotensin converting enzyme inhibition (ACEI, 2.10(-6) mol.kg-1 quinapril i.v.), combined ACEI and cyclooxygenase inhibition (CYOI, 2.8.10(-5) M indomethacin), and endothelin (ET) receptor blockade (10(-6) M BQ 123 and IRL 1038) diminished preglomerular vasodilation (C and JM) caused by URO infusion. Efferent vasoconstriction (C and JM) caused by URO was exaggerated by blockade of nitric oxide synthesis (10(-5) M L-NAME) and abolished by combined ACEI and CYOI, by bradykinin receptor blockade (4.10(-8) M Hoe 140), and by ET blockade. CYOI attenuated only JM efferent constriction. Our results show that URO and ANF possess equipotent vascular and similar natriuretic effects in the rat kidney. The magnitude of preglomerular vasodilation, which is directly mediated by these peptides, depends on the basal level of endogenous vasoconstrictors, while efferent vasoconstriction may be mediated by the secondary release of ET.
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PMID:Effects of urodilatin in the rat kidney: comparison with ANF and interaction with vasoactive substances. 764 24

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.
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PMID:Activated human polymorphonuclear leukocytes elicit endothelium-dependent contraction in isolated pig coronary arteries. 768 46

To elucidate the cause of low prostacyclin (PGI2) production in severe preeclampsia (PE), we studied the activities of phospholipase A2, cyclooxygenase, and PGI2 synthase in umbilical venous endothelial cells obtained from healthy pregnant women and from patients with mild or severe PE. Umbilical venous endothelial cells homogenized in a buffer solution were analysed by calculating the apparent Vmax (mean +/- SEM: p mol/min mg protein) and Km (mean +/- SEM: microM) values for phospholipase A2 activity by the release of arachidonic acid from phosphatidylcholine, for the activity of a complex of cyclooxygenase and PGI2 synthase by the conversion of arachidonic acid to PGI2, and the activity of PGI2 synthase by conversion of PGH2 to PGI2. The phospholipase A2 activity of normal-pregnancy cells (Vmax: 17.0 +/- 2.7 Km: 0.26 +/- 0.04) (n = 10) significantly exceeded that of cells from women with either mild PE (5.8 +/- 0.5, 0.12 +/- 0.02) (n = 4) or severe PE (6.3 +/- 2.0, 0.08 +/- 0.03) (n = 5). The apparent combined activity of cyclooxygenase and PGI2 synthase in mild PE (552 +/- 142, 0.29 +/- 0.07) (n = 8) significantly exceeded that of a normal pregnancy (176 +/- 42, 0.76 +/- 0.25) (n = 7), whereas that in severe PE (326 +/- 36, 3.26 +/- 0.78) (n = 3) was significantly lower than that of a normal pregnancy. PGI2 synthase activity in mild PE (305 +/- 50, 0.12 +/- 0.07) (n = 4) exceeded that of a normal pregnancy (220 +/- 45, 0.13 +/- 0.06) (n = 5), whereas that in severe PE (55 +/- 12, 0.16 +/- 0.04) (n = 3) was lower than that of a normal pregnancy. The phospholipase A2 activity in cells of normal pregnant women exceeded that of cells of women with mild or severe PE. The combined activity of cyclooxygenase and PGI2 synthase in a normal pregnancy was lower than in mild PE, but higher than in severe PE. Similar results were found for PGI2 synthase activity; in normal pregnancy the activity was less than in mild PE, but higher than in severe PE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activities of phospholipase A2, cyclooxygenase, and PGI2 synthase of umbilical venous endothelial cells in preeclamptic women. 783 76

Altered macrophage function after thermal injury is associated with increased production of PGE2 and TNF. However, it is not clear why synthesis of both cellular products remains elevated, as PGE2 is a potent inhibitor of TNF secretion. We studied the relationship between PGE2 and TNF synthesis in a murine model of thermal injury, and examined the effect of prostaglandin blockade on splenic macrophage secretion of these mediators of inflammation. LPS-stimulated production of PGE2 was significantly elevated in burn groups compared with sham-burned controls (pg/ml mean(SEM); sham 151(32): burn 597(147), p < 0.01). TNF production was similarly increased after thermal injury (pg/ml mean(SEM); sham 62(20): burn 928(316), p < 0.01). In vitro culture of macrophages with indomethacin augmented LPS stimulated TNF production in sham-burned controls but did not affect synthesis in burn groups, suggesting a loss of PGE2-dependent regulation of TNF synthesis after thermal injury. Direct measurement of TNF secretion as a function of exogenous PGE2 confirmed this dissociation between PGE2 and TNF synthesis, as burned animals displayed a 5-fold reduction in sensitivity to PGE2-induced inhibition of TNF, when compared with sham-burned controls (ID50 PGE2 molar; sham 1.26 x 10(-8): burn 6.43 x 10(-8), p < 0.05). In vivo pretreatment of burn groups with indomethacin for 5 days before assay partially restored sensitivity to the prostaglandin, and significantly down-regulated synthesis of both TNF and PGE2. These data show that thermal injury is associated with a loss of PGE2-dependent down-regulation of TNF synthesis, which accounts at least in part for increased TNF in these animals. In vivo cyclooxygenase blockade partially restored sensitivity to the prostaglandin and consequently down-regulated synthesis of TNF. These data further support existing evidence that suggests a potential therapeutic role for cyclooxygenase blockade after major thermal injury and trauma.
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PMID:Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin. 834 98

The regulatory role of leukotrienes (LT) on human myelopoiesis was investigated. Mononuclear bone marrow cells from 31 healthy donors were cultivated in the presence of suboptimal concentrations of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in semisolid agar. The addition of LTC4 or LTB4 to the cultures dose-dependently stimulated myeloid stem cell proliferation. Maximal effects were observed at 10(-8) mol/L, at which LTC4 induced a 91% +/- 23% (mean +/- SEM; P = .004) and LTB4 a 73% +/- 22% (P = .008) increase in colony formation. In contrast, addition of the LTB4 isomer 5(S), 12(S)-diHETE did not affect the growth. LTD4 exerted a weak potentiating effect on progenitor proliferation (17% +/- 7% growth stimulation at 10(-10) mol/L; P = .034), whereas LTE4 was without consistent effect. Furthermore, LTC4-induced stimulation of colony formation was insensitive to the LTD4 antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide synthase inhibitor CL42A potently suppressed the proliferation of myeloid colonies, a suppression that could be reversed by parallel addition of LTB4 or LTC4. The results suggest that both LTB4 and LTC4 possess strong and specific synergistic stimulatory effects on GM-CSF-induced human myeloid progenitor cell growth.
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PMID:Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor. 838 Jul 23

Using isolated rat kidneys perfused at controlled pressure, we examined a potential role of endothelium-derived relaxing factor (EDRF) in the pressure control of renin secretion. We found that stimulation of EDRF release by acetylcholine (1 mumol/liter) increased mean perfusate flow rates from 15.0 +/- 0.5 to 18.0 +/- 0.5 ml/min per g and average renin secretion rates from 3.5 +/- 0.5 to 16.0 +/- 2.0 ng angiotensin I/h per min per g at a perfusion pressure of 100 mmHg (mean +/- SEM, n = 6). Those effects of acetylcholine were significantly reduced during inhibition of EDRF formation with NG-nitro-L-arginine (100 mumol/liter), but they were not affected with the cyclooxygenase inhibitor indomethacin (10 mumol/liter). Lowering of the perfusion pressure from 100 mmHg to 40 mmHg resulted in an increase of average renin secretion rates from 3.5 +/- 0.5 to 79 +/- 12 ng AngI/h per min per g under control conditions (n = 8), and to 171 +/- 20 ng AngI/h per min per g in the presence of 10 mumol/liter acetylcholine (n = 3). The rise of renin secretion in response to a reduction of the renal artery pressure was markedly attenuated with inhibitors of EDRF formation such as NG-nitro-L-arginine (100 mumol/liter) and related compounds. During inhibition of EDRF formation, addition of sodium nitroprusside (10 mumol/liter) increased mean perfusate flow rates from 12.0 +/- 0.5 to 23.0 +/- 2.0 ml/min per g and average renin secretion rates from 2.0 +/- 0.5 to 18.0 +/- 1.5 ng AngI/h per min per g at 100 mmHg (n = 5). Lowering of the perfusion pressure from 100 mmHg to 40 mmHg under those conditions increased average renin secretion rates to 220 +/- 14 ng AngI/h per min per g (n = 5). Taken together, our findings suggest that EDRF and related activators of soluble guanylate cyclase stimulate renin secretion from isolated kidneys, predominantly at lower perfusion pressure. Moreover, pressure control of renin secretion appears to require the tonical stimulation by intrarenal EDRF.
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PMID:Involvement of endothelium-derived relaxing factor in the pressure control of renin secretion from isolated perfused kidney. 838 97

We studied the effects of serotonin (5-hydroxytryptamine, 5-HT) on glomerular blood flow (GBF) and on renal vessel diameters in the hydronephrotic kidney and in vascular casts of normal kidneys of rats. 5-HT (60 min after local application of 10(-8) mol.liter-1) constricted the arcuate arteries (-10 +/- 2% to -14 +/- 2%, mean +/- SEM), dilated the interlobular arteries (+13 +/- 2%) and afferent arterioles (+17 +/- 3%), and decreased GBF (-44 +/- 5%). In contrast to normal autoregulation, reduction of renal perfusion pressure after local application of 5-HT from 118 +/- 3 mm Hg by 10 and 20 mm Hg reduced GBF by 12 +/- 2% and 23 +/- 3%, respectively. The 5-HT2 antagonist, ritanserin (60 min after local application of 10(-6) mol.liter-1), dilated all preglomerular vessels and increased GBF. In the presence of ritanserin, 5-HT lost nearly all vascular effects. During infusion of 5-HT (5 micrograms.min-1 i.v. for 20 min) vascular reactions were similar to those under local application. After cyclooxygenase inhibition with indomethacin, infusion of 5-HT failed to constrict the arcuate arteries whereas vasodilation of the small preglomerular vessels remained unaffected. Analyzing vascular casts of normal kidneys we observed considerable vascular spasms and an average vasoconstriction of the interlobar arteries of 19 +/- 9% after i.v. infusion of 5-HT. We believe that 5-HT decreases GBF by 5-HT2 receptor-mediated constriction of the large renal vessels which are modulated by the prostaglandin system, whereas 5-HT dilates the small preglomerular vessels, most likely via 5-HT1-like receptors. Furthermore, our data indicate that 5-HT impairs the myogenic component of renal autoregulation in the low pressure range.
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PMID:Visualization of serotonin effects on renal vessels of rats. 844 Dec 28

To study the involvement of local sensory nerves in reactive hyperemia, laser-Doppler measurements of skin blood flow were recorded in locally anesthetized and untreated forearm sites in eight volunteers after 90, 180, and 360 seconds of arrested forearm blood flow. The reactive hyperemia increased in magnitude and duration in response to increasing occlusion periods. However, maximum postocclusion flows in the untreated site of 31 +/- 5%, 38 +/- 6%, and 49 +/- 5% (mean +/- SEM) flux were significantly greater than the 14 +/- 3% (P < .005), 20 +/- 4% (P < .005), and 25 +/- 5% (P < .001) flux seen in the anesthetized sites. The duration of the hyperemia was also shortened from 139 +/- 26 seconds in the untreated site to 61 +/- 17 seconds (after the 360-second occlusion, P < .02) in the anesthetized sites. The anesthesia did not alter the increase in local blood flow induced by intradermally injected calcitonin gene-related peptide. Topically applied capsaicin induced a localized increase in blood flow that was unaffected by anesthesia and a surrounding flare that was abolished by the treatment. The results show that local anesthesia can significantly inhibit reactive hyperemia by a mechanism that does not alter the vasodilation induced by exogenous calcitonin gene-related peptide or the localized capsaicin-induced release of vasodilators from sensory nerves. Indomethacin was also found to be effective in suppressing reactive hyperemia. The evidence suggests that postocclusion reactive hyperemia in human forearm skin is mediated by a local reflex involving sensory nerves and a cyclooxygenase product, probably a vasodilator prostaglandin.
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PMID:Evidence for sensory nerve involvement in cutaneous reactive hyperemia in humans. 850 26

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