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

Linkage analysis studies previously identified genetic loci associated with proteinuria and hypertension on chromosome 1 of fawn-hooded hypertensive (FHH) rats. The present studies were performed on conscious male and female rats to evaluate the influence of transfer of chromosome 1 from the Brown Norway (BN) rat to the FHH genetic background (FHH-1BN). Rats were maintained for 2 wk on 8.0% NaCl chow with NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (12.5 mg/l) to induce hypertension and accelerate the onset of renal disease. Mean arterial blood pressure (MAP) was significantly higher in the male FHH (188 +/- 3 mmHg, n = 13) compared with the BN (121 +/- 3 mmHg, n = 8); MAP in the FHH-1(BN) was midway between the two parental strains (167 +/- 5 mmHg, n = 9). Urinary protein and albumin excretion rates in the male FHH-1(BN) (Uprot = 189 +/- 36 mg/day, Ualb = 69 +/- 16 mg/day, n = 10) were also midway between levels observed in the FHH (Uprot = 485 +/- 54 mg/day; Ualb = 206 +/- 25 mg/day, n = 13) and the BN (Uprot = 32 +/- 5 mg/day, Ualb = 5 +/- 1 mg/day, n = 8). Creatinine clearance was elevated, and the degree of glomerular damage was significantly reduced in the FHH-1BN compared with the FHH. Qualitatively similar results were obtained from female FHH, FHH-1BN, and BN rats. The present results indicate that genes contributing to l-NAME-induced hypertension and renal disease are found on chromosome 1 of the FHH rat.
 ...
PMID:Substitution of chromosome 1 ameliorates L-NAME hypertension and renal disease in the fawn-hooded hypertensive rat. 1564 86

Extracellular matrix molecules such as elastin and collagens provide mechanical support to the vessel wall. In addition to its structural role, elastin is a regulator that maintains homeostasis through biologic signaling. Genetically determined minor modifications in elastin and collagen in the aorta could influence the onset and evolution of arterial pathology, such as hypertension and its complications. We previously demonstrated that the inbred Brown Norway (BN) rat shows an aortic elastin deficit in both abdominal and thoracic segments, partly because of a decrease in tropoelastin synthesis when compared with the LOU rat, that elastin gene polymorphisms in these strains do not significantly account for. After a genome-wide search for quantitative trait loci (QTL) influencing the aortic elastin, collagen, and cell protein contents in an F2 population derived from BN and LOU rats, we identified on chromosomes 2 and 14, 3 QTL specifically controlling elastin levels, and a further highly significant QTL on chromosome 17 linked to the level of cell proteins. We also mapped 3 highly significant QTL linked to body weight (on chromosomes 1 and 3) and heart weight (on chromosome 1) in the cross. This study demonstrates the polygenic control of the content of key components of the arterial wall. Such information represents a first step in understanding possible mechanisms involved in dysregulation of these parameters in arterial pathology.
Hypertension 2005 Mar
PMID:Chromosomal mapping of quantitative trait loci controlling elastin content in rat aorta. 1566 57

Dahl salt-sensitive (SS) and consomic, salt-resistant SS-13(BN) rats possess substantial differences in blood pressure salt-sensitivity even with highly similar genetic backgrounds. The present study examined whether increased oxidative stress, particularly H2O2, in the renal medulla of SS rats contributes to these differences. Blood pressure was measured using femoral arterial catheters in three groups of rats: 1) 12-wk-old SS and consomic SS-13(BN) rats fed a 0.4% NaCl diet, 2) SS rats fed a 4% NaCl diet and chronically infused with saline or catalase (6.9 microg x kg(-1) x min(-1)) directly into the renal medulla, and 3) SS-13(BN) fed high salt (4%) and infused with saline or H2O2 (347 nmol x kg(-1) x min(-1)) into the renal medullary interstitium. After chronic blood pressure measurements, renal medullary interstitial H2O2 concentration ([H2O2]) was collected by microdialysis and analyzed with Amplex red. Blood pressure and [H2O2] were both significantly higher in SS (126 +/- 3 mmHg and 145 +/- 17 nM, respectively) vs. SS-13(BN) rats (116 +/- 2 mmHg and 56 +/- 14 nM) fed a 0.4% diet. Renal interstitial catalase infusion significantly decreased [H2O2] (96 +/- 41 vs. 297 +/- 52 nM) and attenuated the hypertension (146 +/- 2 mmHg catalase vs. 163 +/- 4 mmHg saline) in SS rats after 5 days of high salt (4%). H2O2 infused into the renal medulla of consomic SS-13(BN) fed high salt (4%) for 7 days accentuated the salt sensitivity (145 +/- 2 mmHg H2O2 vs. 134 +/- 1 mmHg saline). [H2O2] was also increased in the treated group (83 +/- 1 nM H2O2 vs. 44 +/- 9 nM saline). These data show that medullary production of H2O2 may contribute to salt-induced hypertension in SS rats and that chromosome 13 of the Brown Norway contains gene(s) that protect against renal medullary oxidant stress.
 ...
PMID:Effect of renal medullary H2O2 on salt-induced hypertension and renal injury. 1610 3

To determine circulating angiotensin-(1-7) [Ang-(1,7)] levels in rats with different angiotensin converting enzyme (ACE) genotypes and to evaluate the effect of hypertension on levels of this heptapeptide, plasma levels of angiotensin II (Ang II) and Ang-(1-7) were determined by HPLC and radioimmunoassay in (a) normotensive F0 and F2 homozygous Brown Norway (BN; with high ACE) or Lewis (with low ACE) rats and (b) in hypertensive F2 homozygous male rats (Goldblatt model). Genotypes were characterized by PCR and plasma ACE activity measured by fluorimetry. Plasma ACE activity was 2-fold higher (p < 0.05) in homozygous BN compared to homozygous Lewis groups. In the Goldblatt groups, a similar degree of hypertension and left ventricular hypertrophy was observed in rats with both genotypes. Plasma Ang II levels were between 300-400% higher (p < 0.05) in the BN than in the Lewis rats, without increment in the hypertensive animals. Plasma Ang-(1-7) levels were 75-87% lower in the BN rats (p < 0.05) and they were significantly higher (p < 0.05) in the hypertensive rats from both genotypes. Plasma levels of Ang II and Ang-(1-7) levels were inversely correlated in the normotensive rats (r = -0.64; p < 0.001), but not in the hypertensive animals. We conclude that there is an inverse relationship between circulating levels of Ang II and Ang-(1-7) in rats determined by the ACE gene polymorphism. This inverse relation is due to genetically determined higher ACE activity. Besides, plasma levels of Ang-(1-7) increase in renovascular hypertension.
 ...
PMID:Effect of hypertension on angiotensin-(1-7) levels in rats with different angiotensin-I converting enzyme polymorphism. 1622 62

In humans and rats, angiotensin I-converting enzyme activity is significantly determined by a gene polymorphism. Homozygous Brown Norway rats have higher plasma angiotensin I-converting enzyme activity and circulating angiotensin II (Ang II) levels than Lewis rats. Because Ang II induces NAD(P)H oxidase activation, we hypothesized here that Brown Norway rats have higher vascular NAD(P)H oxidase activity and superoxide anion production than Lewis rats. Homozygous Brown Norway (n=15) and Lewis (n=13) male rats were used. Plasma angiotensin I-converting enzyme activity (by fluorimetry), Ang II levels (by high-performance liquid chromatography and radioimmunoassay), and aortic NAD(P)H oxidase activity, as well as superoxide anion production (by chemiluminescence with lucigenin) were measured. Plasma angiotensin I-converting enzyme activity and Ang II levels were 100% higher in Brown Norway rats than in Lewis rats (P<0.05). Aortic angiotensin I- converting enzyme, but not Ang II, was elevated (P<0.05). Aortic superoxide anion production and NAD(P)H oxidase activity were 300% and 260% higher in Brown Norway than in Lewis rats, respectively (P<0.05), which was not observed in Brown Norway rats treated with candesartan (10 mg/kg per day for 7 days). Endothelial NO synthase activity in the aorta from Brown Norway rats was significantly lower than in Lewis rats. However, inducible NO synthase activity and both endothelial NO synthase and inducible NO synthase mRNA and protein levels were similar in both genotypes. In summary, Brown Norway rats have higher vascular NAD(P)H oxidase activity and superoxide anion production than Lewis rats, suggesting the presence of a higher level of vascular oxidative stress in rats with genetically higher angiotensin I-converting enzyme levels. This effect is mediated through the angiotensin I receptor.
Hypertension 2005 Dec
PMID:Increased aortic NADPH oxidase activity in rats with genetically high angiotensin-converting enzyme levels. 1623 May 8

Elevated plasma homocysteine (Hcys) has been reported to participate in the development of arterial and glomerular sclerosis in Dahl salt-sensitive hypertensive (SS) rats. The mechanism resulting in hyperhomocysteinemia in these animals remains unknown. Disposal of Hcys in the kidneys plays an important role in regulating the plasma Hcys level. We, therefore, examined the activities and expressions of the enzymes involved in the metabolism of Hcys in the kidneys of SS rats, compared with that of Brown Norway rats and SSBN13 rats, a consomic subcolony of SS rats that carries a substituted chromosome 13 from Brown Norway rats. High-performance liquid chromatography analysis demonstrated that plasma Hcys levels were significantly higher in SS rats. The conversion of S-adenosylhomocysteine into Hcys via S-adenosylhomocysteine hydrolase by renal tissue was not different among these 3 rat strains. However, the metabolic rate of Hcys into cysteine was markedly reduced in the SS rat kidneys. The mRNA and protein levels of cystathionine beta-synthase (CBS), one of the key enzymes in the transsulfuration pathway in the kidneys, were significantly lower in SS rats. In microdissected nephron segments, CBS mRNA was shown to be mainly present in renal proximal tubules (PTs). The mRNA levels of CBS in the PTs were also significantly decreased in SS rats, accompanied by a reduced CBS activity in PTs. We conclude that hyperhomocysteinemia is associated with a decreased activity and expression of CBS in renal PTs because of the defect of chromosome 13 in SS rats.
Hypertension 2006 Jun
PMID:Hyperhomocysteinemia associated with decreased renal transsulfuration activity in Dahl S rats. 1663 97

It has been suggested that the effects of angiotensin II type 1 receptor (AT1R) blockers are in part because of angiotensin II type 2 receptor (AT2R) signaling. Interactions between the AT2R and kinins modulate cardiovascular function. Because AT2R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT1R blocker valsartan and the ACE inhibitor benazepril require AT2R signaling through the bradykinin 1 and 2 receptors (B1R and B2R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT2R inhibitor), valsartan+des-arg9-[Leu8]-bradykinin (B1R inhibitor), valsartan+HOE140 (B2R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT2R, B1R, or B2R in the presence of valsartan prevented the reduction seen with valsartan alone. B2R blockade inhibited the effect of benazepril. Injury increased AT1R, AT2R, B1R, and B2R expression. Treatment with valsartan but not benazepril significantly increased intima AT2R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT2R, B1R, and B2R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT2R, B1R, and B2R. Results suggest that AT2R expression and increased cGMP represent a molecular mechanism that differentiates AT1R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.
Hypertension 2006 Nov
PMID:Angiotensin II type 2 receptor expression after vascular injury: differing effects of angiotensin-converting enzyme inhibition and angiotensin receptor blockade. 1698 65

By continuous monitoring of abdominal aortic blood pressure via telemetry in conscious rats, we have observed that systolic, diastolic, and pulse pressures of male Brown-Norway rats were all significantly lower than that of male Wistar-Kyoto rats, despite the fact that all of the values in both strains were within normotensive ranges. Further analyses performed in 166 animals from the progeny of an F2 intercross between Brown-Norway and Wistar-Kyoto rats revealed that, despite a high correlation between systolic blood pressure and diastolic blood pressure, there was no correlation between pulse pressure and diastolic blood pressure, and the value of the correlation between systolic blood pressure and pulse pressure was lower than that of systolic blood pressure with diastolic blood pressure. Two major and highly significant (P<0.001) quantitative trait loci linked to pulse pressure were found on chromosome 4 (Pp1) and 16 (Pp2). Only suggestive quantitative trait loci were found for systolic blood pressure, but the strongest one (Sbp1) had the same peak and linkage probability profile as Pp1. Altogether, these data show that genetic determinants affecting pulse pressure in normotensive animals are either stronger or independent from the ones affecting systolic blood pressure and are of interest in light of evidence showing that pulse pressure is highly heritable in humans and that elevated pulse pressure is a predictor of cardiovascular risk.
Hypertension 2006 Nov
PMID:Genetic determinants of systolic and pulse pressure in an intercross between normotensive inbred rats. 1701 78

The aim of the present study was to evaluate the effects of the prostaglandin F2 alpha analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes. Rodents have been increasingly used in glaucoma research; however, conflicting results regarding the actions of prostaglandins on rodent IOP have been published. In Wistar rats, a single dose of latanoprost (60 ng) produced a biphasic change in IOP: an initial rise in pressure (2.1+/-0.7 mmHg) peaking at 2 h, followed by a prolonged hypotension with a peak reduction in IOP (5.2+/-0.7 mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose-related with ED50 values of 108 and 5.2 ng, respectively. These responses were antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6 mice, a single dose of latanoprost also produced a biphasic response in IOP with an initial rise in pressure peaking between 1 and 2 h, followed by prolonged hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP response to topical latanoprost is characterized by an initial hypertension followed by a prolonged hypotension. This prolonged hypotension is similar to that measured in monkeys and humans. Taken together, these results support the idea that rodents can serve as in vivo models to study the actions of ocular hypotensive agents, such as prostaglandins.
 ...
PMID:Effects of latanoprost on rodent intraocular pressure. 1702 54

Rats are employed to investigate the role of platelets in thrombus formation under flow conditions in vivo and to evaluate the pre-clinical potential of antiplatelet drugs. While Wistar and Sprague-Dawley (SD) strains are commonly used in thrombosis models, a number of rat strains have been established. Each strain possesses genetically unique characteristics such as hypertension, hyperglycemia or hyperlipidemia. The appropriate selection of a strain might have advantages for physiological and pharmacological studies. Comparative investigation of platelet aggregation among laboratory strains of rats is useful for the development of thrombosis models. In the present study, platelet aggregation response in eight laboratory rat strains, ACI, Brown Norway (BN), Donryu, Fischer 344 (F344), LEW, SD, Wistar and WKAH, were compared. Considerable strain differences were observed in ADP-, collagen- and TRAP-induced platelet aggregation. SD and BN are high-platelet-aggregation strains, while F344 and ACI are low-response strains. In the arteriovenous shunt thrombosis model, SD formed larger thrombi than F344 and Wistar rats. In the FeCl(3)-induced thrombosis model with the carotid artery, the time to occlusion of SD was significantly shorter than of F344 and ACI rats. F344 and ACI rats had significantly increased bleeding times compared with SD rat. The present study demonstrates that there are considerable strain differences in platelet aggregation among laboratory rats, which reflect thrombus formation.
 ...
PMID:Genetic strain differences in platelet aggregation and thrombus formation of laboratory rats. 1739 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>