Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelins are a recently discovered family of potent contractile peptides produced by endothelial cells. These peptides have been suggested to play an important role in the pathogenesis of hypertension, myocardial infarction, cardiogenic shock, and so on. The aim of our study was to compare the responses to endothelin-1 (ET-1) with those to L-noradrenaline (NA) in aortic rings from rats of different strains and ages. Thoracic aorta rings from spontaneously hypertensive (SHR), Wistar Kyoto (WKY), Brown Norway (BN) and spontaneously hyperlipemic (Yoshida, YOS) rats 2-4 (young), 6-8 (adult) and 20-25 (old) months old were used. There were no changes in the pD2 values for ET-1 and NA between WKY and SHR rats at the ages studied. The ET-1 and NA Emax in adult SHR rats was significantly lower than in the age-matched WKY animals. Old age reduced the ET-1 and NA Emax in both SHR and WKY rats abolishing the difference observed at 6-8 months in the same groups. The reactivity to ET-1 and NA of BN and YOS rats was modified only in young rats. In YOS strain aging did not modify the ET-1 and NA responses as the pD2 and Emax values remained unchanged. Our findings demonstrate that ET-1 is a more potent vasoconstrictor than NA and that this potency remains unchanged throughout the ages and the pathologies studied. In contrast, the pD2 of NA decreases with old age in SHR and WKY rats. We conclude that rat strain but not hypertension or hyperlipemia can modify the response to ET-1 or NA in old age. We suppose that this functional change may involve alterations in the responsiveness of vascular smooth muscle.
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PMID:Aging and in vitro vascular responses to endothelin-1 in several rat strains. 810 9

The physiological activator of protein kinase C (PKC), diacylglycerol, is formed by hydrolysis of phosphoinositides (PI) by phospholipase C (PLC) or phosphatidylcholine by phospholipase D (PLD). We have measured activation of these phospholipases by endothelin-1 (ET-1), bradykinin (BK), or phenylephrine (PE) in ventricular myocytes cultured from neonatal rat. The stimulation of PI hydrolysis after 10 min by 0.1 microM ET-1 (about 12-fold) was much greater than for BK or PE (each about four-fold), and did not correlate with translocation of nPKC delta or nPKC epsilon (Clerk A. Bogoyevitch MA. Andersson MB. Sugden PH, 1994. J Biol Chem 269: 32848-32857: Clerk A, Gillespie-Brown J, Fuller SJ, Sugden PH, 1996. Biochem J 317: 109-118). However, ET-1 and BK stimulated a similar rapid increase in [3H]InsP, formation (< 30 s), which was much greater than that seen with PE. This early phase correlated with PKC translocation. Acute or chronic exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) or treatment with Ro-31-8220 showed that the stimulation of PI hydrolysis by PE, but not ET-1 or BK, was inhibited by activation of PKC. Furthermore, ET-1 and BK heterologously desensitized the stimulation of PI hydrolysis by PE, ET-1 or BK homologously uncoupled their own receptors from [3H]InsP3 formation, but there was no evidence of heterologous desensitization with these two agonists. Anomalously, chronic exposure to TPA increased the stimulation of PI hydrolysis by BK, but this probably resulted from an increase in BK receptor density. PLD was also rapidly activated by TPA. ET-1, BK or PE. Experiments with Ro-31-8220 showed that the stimulation of PLD by ET-1 and BK was mediated through activation of PKC. We discuss the characteristics of the activation of PI hydrolysis and PLD by ET-1, BK, and PE with respect to the translocation of PKC.
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PMID:Regulation of phospholipases C and D in rat ventricular myocytes: stimulation by endothelin-1, bradykinin and phenylephrine. 922 Mar 45

The objective of this study is to investigate if endothelin-1 (ET-1) gene expression changes during the early response phase following antigen challenge. We used sensitized Brown-Norway rats known to develop an early airway response after antigen challenge. After ovalbumin challenge, sensitized rats presented an early response, characterized by an increase in pulmonary pressure (209+/-14.53%,P<0. 01) and diminished functional parameters (inspiratory capacity, forced vital capacity (FVC) and expiratory flow at 75% of FVC), compared to their respective basal values. ET-1 mRNA expression was assessed by reverse transcription and polymerase chain reaction using specific primers for prepro-ET-1. A group of unsensitized rats was used as control. ET-1 expression was significantly enhanced in sensitized rats during the early response (290+/-62%,P<0.01) compared to the control group. In conclusion, antigen challenge induces an activation of ET-1 gene expression during the early response in Brown-Norway rats, suggesting a contribution of this protein to the development of bronchoconstriction.
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PMID:Endothelin-1 expression during early response after antigen challenge in brown-norway rats. 991 59

The objective of the present study was to evaluate age-related changes in the protein and gene expression of modulators of erectile function (nitric oxide [NO] and endothelin-1 [ET-1]) and growth factors such as transforming growth factor (TGF-beta1) and vascular endothelial growth factor (VEGF) in the penile tissue of Brown-Norway (BN) rats. Young and old BN male rats were euthanized, and the penile tissue was processed for immunohistochemical and molecular analyses. Total RNA was extracted, and an Access reverse transcription-polymerase chain reaction (RT-PCR) system was used for messenger RNA (mRNA) expression analysis. Immunohistochemical studies showed a decreased expression of endothelial nitric oxide synthase (eNOS) protein and an increased staining for ET-1. Quantitative analysis of PCR products revealed decreased levels of VEGF mRNA expression in the old population of rats. The most significant decrease was detected between bands corresponding to splice forms 164 (21%) and 120 (18%). The observed alterations in the gene expression of growth factors such as VEGF may contribute to the abnormal age-related morphological and physiological alterations in the erectile tissue.
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PMID:Altered growth factor expression in the aging penis: the Brown-Norway rat model. 1200 41

The purpose of this study was to determine whether endothelin B (ETB) receptor levels in the optic nerve are related to retinal ganglion cell (RGC) loss in a model of chronic endothelin-1 (ET-1) induced optic neuropathy. RGCs of adult Brown Norway rats were first retrogradely labeled with fluorochrome from the superior colliculi. An osmotic minipump was surgically implanted 7 days later to deliver 10(-11) M (n = 9), 10(-9) M (n = 12) or 10(-7) M (n = 9) ET-1 to the retrobulbar optic nerve for 28 days. RGC survival was expressed as the ratio of RGC counts in experimental versus control eyes in wholemounted retinas. Optic nerves were used for either ETB western blot analysis (n = 24) or immunohistochemistry (n = 6) for ETB and glial fibrillary acidic protein (GFAP) to localize astrocytes. ETB expression was higher in the experimental nerve compared to the fellow untreated control nerve in 19 (79%) of the 24 animals with a mean increase of 16.7 +/- 4.5% in densitometric analyses of the immunoblots. Experimental nerves showed stronger labeling for both ETB and GFAP compared to control nerves. ETB-positive cells almost completely co-localized with GFAP-positive cells in both experimental and untreated control nerves, however, ETB expression was stronger in the astrocyte soma and proximal processes, while GFAP was expressed more strongly in the distal processes. There was a weak relationship between RGC loss and increase in ETB expression (r = -0.417, p = 0.076). There is an upregulation of ETB expression in optic nerve astrocytes in ET-1 induced chronic optic neuropathy causing RGC loss.
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PMID:Increase in endothelin B receptor expression in optic nerve astrocytes in endothelin-1 induced chronic experimental optic neuropathy. 1893 60

Aging adults are a growing segment of the U.S. population and are likely to exhibit increased susceptibility to many environmental toxicants. However, there is little information on the susceptibility of the aged to toxicants. The toxicity of toluene has been well characterized in young adult rodents but there is little information in the aged. Three approaches were used: (1) pharmacokinetic (PK), (2) cardiac biomarkers, and (3) whole-animal physiology to assess whether aging increases susceptibility to toluene in the Brown Norway (BN) rat. Three life stages, young adult, middle aged, and aged (4, 12, and 24 mo, respectively), were administered toluene orally at doses of 0, 0.3, 0.65, or 1 g/kg and subjected to the following: terminated at 45 min or 4 h post dosing, and blood and brain toluene concentration were measured; terminated at 4 h post dosing, and biomarkers of cardiac function were measured; or monitor heart rate (HR), core temperature (Tc), and motor activity (MA) by radiotelemetry before and after dosing. Brain toluene concentration was significantly elevated in aged rats at 4 h after dosing with either 0.3 or 1 g/kg. Blood toluene concentrations were unaffected by age. There were various interactions between aging and toluene-induced effects on cardiac biomarkers. Most notably, toluene exposure led to reductions in mRNA markers for oxidative stress in aged but not younger animals. Toluene also produced a reduction in cardiac endothelin-1 in aged rats. Higher doses of toluene led to tachycardia, hypothermia, and a transient elevation in MA. Aged rats were less sensitive to the tachycardic effects of toluene but showed a prolonged hypothermic response. Elevated brain levels of toluene in aged rats may be attributed to their suppressed cardiovascular and respiratory responses. The expression of several cardiac biochemical markers of toluene exposure in the aged may also reflect differential susceptibility to this toxicant.
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PMID:Aging and susceptibility to toluene in rats: a pharmacokinetic, biomarker, and physiological approach. 2007 99

The SS-16(BN)/Mcwi consomic rat was produced by the introgression of chromosome 16 from the Brown Norway (BN/NHsdMcwi) rat onto the genetic background of the Dahl salt-sensitive (SS/Mcwi) rat by marker-assisted breeding. We have previously shown that the normotensive SS-16(BN)/Mcwi consomic strain is better protected from developing left ventricular dysfunction and fibrosis with aging than the hypertensive SS/Mcwi parental strain; however, the mechanism of this protection was not clear since the SS-16(BN)/Mcwi had both lowered blood pressure and an altered genetic background compared with SS/Mcwi. Microarray analysis of SS-16(BN)/Mcwi and SS/Mcwi left ventricle tissue and subsequent protein pathway analysis were used to identify alterations in gene expression in signaling pathways involved with the observed cardioprotection on the SS background. The SS-16(BN)/Mcwi rats exhibited much higher mRNA levels of expression of transcription factor JunD, a gene found on chromosome 16. Additionally, high levels of differential gene expression were found in pathways involved with angiogenesis, oxidative stress, and growth factor signaling. We tested the physiological relevance of these pathways by experimentally determining the responsiveness of neonatal cardiomyocytes to factors from identified pathways and found that cells isolated from SS-16(BN)/Mcwi rats had a greater growth response to epidermal growth factor and endothelin-1 than those from parental SS/Mcwi. We also demonstrate that the SS-16(BN)/Mcwi is better protected from developing fibrosis with surgically elevated afterload than other normotensive strains, indicating that gene-gene interactions resulting from BN chromosomal substitution confer specific cardioprotection. When combined with our previous findings, these data suggest that that SS-16(BN)/Mcwi may have an increased angiogenic potential and better protection from oxidative stress than the parental SS/Mcwi strain. Additionally, the early transient idiopathic left ventricular hypertrophy in the SS-16(BN)/Mcwi may be related to altered myocyte sensitivity to growth factors.
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PMID:Mechanisms of cardioprotection resulting from Brown Norway chromosome 16 substitution in the salt-sensitive Dahl rat. 2275 22

Aging leads to progressive pathophysiological changes in blood vessels of the brain and periphery. The aim of this study was to evaluate the effects of aging on cerebral vascular function and structure. Basilar arteries were isolated from male Fischer 344 cross Brown Norway (F344xBN) rats at 3, 8, and 24 months of age. The basilar arteries were cannulated in the pressurized system (90 cm H2O). Contractile responses to KCl (30-120 mmol/L) and endothelin-1 (10(-11)-10(-7) mol/L) were evaluated. Responses to acetylcholine (ACh) (10(-10)-10(-4) mol/L), diethylamine (DEA)-NONO-ate (10(-10)-10(-4) mol/L), and papaverin (10(-10)-10(-4) mol/L) were assessed to determine both endothelium-dependent and endothelium-independent responsiveness. Advanced aging (24 months) decreased responses of the basilar artery to both the contractile and relaxing agents; whereas, DEA-induced dilation was significantly higher in the 8-month-old group compared with the younger and older groups. The arterial wall-to-lumen ratio was significantly increased in 24-month-old rats. Smooth muscle cell count was also decreased in old rats. These findings indicate that aging produces dysfunction of both the endothelium and the vascular smooth muscle in the basilar artery. Aging also alters wall structure of the basilar artery, possibly through decreases in smooth muscle cell number and concomitant hypertrophy.
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PMID:The effects of aging on the functional and structural properties of the rat basilar artery. 2490 95