Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of chronic treatment with the specific AT1 angiotensin receptor antagonist, irbesartan, or the angiotensin converting enzyme inhibitor, enalapril, were assessed in uninephrectomized fawn-hooded hypertensive rats (FHH) and compared with vehicle treatment. Three days after uninephrectomy, irbesartan (240 mg/liter), enalapril (80 mg/liter) or vehicle were administered via the drinking water. Systolic blood pressure (SBP) and protein excretion rates (UprotV) were determined monthly. In rats receiving irbesartan (N = 7) and enalapril (N = 6) SBP (132 +/- 3 mm Hg and 133 +/- 6, respectively) was essentially normalized at 12 weeks when compared with vehicle (169 +/- 6 mm Hg (N = 6); all comparisons were P < 0.05 by ANOVA). Similarly, proteinuria was lower in irbesartan (44 +/- 12 mg/day) and enalapril (19 +/- 2) groups versus vehicle (123 +/- 10 mg/day). Treatment with both drugs was associated with marked reduction in glomerulosclerosis at 12 weeks (both < 5% vs. vehicle, 43 +/- 9%) without effect on glomerular volume. In identically prepared rats, glomerular capillary hydraulic pressure (PGC, estimated from stop-flow pressure, Psf) was lower in FHH receiving irbesartan (58 +/- 1 mm Hg, N = 6) or enalapril (54 +/- 2, N = 6) than in vehicle-treated rats, in whom PGC was greatly elevated (68 +/- 2 mm Hg; N = 7). Despite this, GFR and single nephron GFR were well maintained. These data support a critical role for AT1 receptor-mediated, angiotensin-dependent processes in the pathogenesis of hypertension in FHH, and further implicate elevated PGC as a major determinant of glomerular injury in this model.
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PMID:The angiotensin receptor antagonist, irbesartan, reduces renal injury in experimental chronic renal failure. 894 34

The spontaneously hypertensive fawn-hooded rat (FHH) develops accelerated albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by moderate systemic hypertension, a relatively low afferent to efferent arteriolar resistance ratio, and glomerular hypertension. The FHH study presented here was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in ameliorating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (PGC) Untreated rats developed hypertension and high PGC, and all (N = 22) except one died of ESRD within the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i prevented development of systemic and glomerular hypertension, and it largely prevented proteinuria and FGS; all rats survived throughout the follow-up period. Rats treated with late-onset (22 wk) ACE-i were hypertensive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and PGC but could not fully prevent some hypertension, albuminuria, and FGS at the later stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blood pressure and development of FGS during therapy, but after withdrawal of ACE-i, systemic and glomerular hypertension developed as in untreated animals. This regimen postponed but did not control FGS development and early mortality. The results of this study indicate that: (1) early-onset ACE-i very effectively protects against development of renal damage in the FHH; (2) this protection is associated with normalization of the elevated glomerular capillary pressure; (3) ACE-i cannot completely prevent further development of previously established FGS, despite lowering glomerular capillary pressure; (4) early-temporary ACE-i has no long-term controlling effect on arterial and glomerular pressure, and it cannot control development of FGS.
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PMID:Angiotensin-converting enzyme inhibition in the prevention and treatment of chronic renal damage in the hypertensive fawn-hooded rat. 904 44

To evaluate the presence of hyperfiltration in two-kidney, one clip (2K, 1C) Goldblatt hypertensive rats, micropuncture studies of the unclipped kidney were used to examine renal functional reserve (RFR) with glycine (G) infusion in normal (N) rats and 2K, 1C rats. Systemic hypertension in 2K, 1C rats was associated with significantly increased values of single-nephron glomerular filtration rate (SNGFR), glomerular plasma flow (QA) and glomerular capillary hydrostatic pressure (PGC) when compared with N rats. Glycine infusion produced a marked increase in SNGFR, QA and whole-kidney GFR in N rats. In contrast, no changes were observed in these parameters in 2K, 1C rats. Lack of response in 2K, 1C rats was related to the failure of renal vessels to dilate during G infusion. These results suggest that loss of renal functional reserve in systemic hypertension is dependent on an abnormal function of renal vascular resistances.
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PMID:Evaluation of renal functional reserve of contralateral kidney of two-kidney, one clip Goldblatt hypertensive rats. 1536 35

The peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) is a novel transcriptional co-activator that holds an important role in lipid and glucose metabolism. PGC-1alpha is a candidate gene for the metabolic syndrome (MS) as well as type 2 diabetes. Recent studies suggested linkage between the chromosomal region of PGC-1alpha and fasting serum insulin levels, and associates a Gly482Ser polymorphism of the gene with type 2 diabetes and hypertension. In this study, we investigated whether the Gly482Ser variant is associated with the MS per se or other phenotypic traits related to this syndrome. The variant was examined, using PCR-RFLP, in the DanMONICA cohort comprising a population-based sample of 2349 subjects. MS was defined using the National Cholesterol Education Program -- Adult Treatment Panel III (NCEP-ATPIII) criteria. The allelic frequency of the Ser482 allele was 35.8% in the MS group and 35.6% in the non-MS group (P = 0.74). There were no significant differences across the three groups of genotypes with respect to any of the examined variables, including BMI, waist, fasting serum lipids, plasma glucose, serum insulin, HOMA estimates of insulin resistance and insulin secretion, 24-ambulatory blood pressure or left ventricular mass index. In conclusion, the Gly482Ser polymorphism of the PGC-1alpha gene is not associated with the metabolic syndrome, related quantitative traits or cardiac hypertrophy among Danish Caucasian subjects.
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PMID:Studies of the Gly482Ser polymorphism of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) gene in Danish subjects with the metabolic syndrome. 1564 78

PGC-1alpha is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of PGC-1alpha has previously shown association with arterial hypertension among Austrian men. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial hypertension were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of hypertension and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for hypertension compared with Gly/X carriers (P=0.001). In conclusion, the Ser allele of PGC-1alpha Gly482Ser confers a significantly reduced risk of hypertension in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women.
Hypertension 2005 Apr
PMID:PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites. 1573 46

To investigate whether variations in the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) are associated with essential hypertension and type 2 diabetes in a Chinese population. A case-control study design was applied in a Chinese population. Two single nucleotide polymorphisms (SNPs), +1302G>A and G482S, in the PGC-1alpha gene were genotyped and compared between 494 unrelated Chinese subjects with essential hypertension and type 2 diabetes and 555 normal control subjects with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. These two polymorphisms were in highly significant linkage disequilibrium with each other (p <0.0001). The frequency of the 482S allele was 42.9% in the Chinese population, which was similar to the frequency in the Japanese population (43.7%), but much higher than those of Caucasian populations (30.8% to 38.1%). There were no associations of the G482S and +1302G>A polymorphisms and haplotype combinations with essential hypertension and type 2 diabetes. In addition, no associations were found between these two polymorphisms and blood pressure. In conclusion, these results indicated that these two variations in the PGC-1alpha gene might not contribute to the risk of hypertension and type 2 diabetes in the Chinese population studied here.
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PMID:Peroxisome proliferator-activated receptor-gamma coactivator-1alpha polymorphism is not associated with essential hypertension and type 2 diabetes mellitus in Chinese population. 1582 63

Our objective was to search for differences in genotypes of peroxisome proliferator-activated receptor gamma (PPARgamma) (Pro12 Ala) and its coactivator PGC-1alpha (Gly482 Ser) in adolescents harboring features of metabolic syndrome. In a population-based study, we determined medical history, anthropometric variables, biochemical measurements and arterial blood pressures of 934 high-school students of Caucasian origin. We selected 220 adolescents who had systolic or diastolic blood pressures more than the 80th or less than the 20th percentiles based on the previous single set of measurements. One hundred and seventy-five adolescents completed the study and underwent two additional blood pressure measurements on different days, as well as biochemical analysis and genotyping. We found no association between insulin resistance, body mass index (BMI) and leptin levels and PPARgamma and PGC-1alpha genotypes. The 12 Ala PPARgamma allele was associated with increased waist-to-hip ratio (WHR) and carriers seemed to have higher diastolic blood pressure and lower pulse pressure than non-carriers, particularly in the hypertensive and overweight group. Although Ser482 Ser PGC-1alpha homozygotes had lower WHRs than other PGC-1alpha genotypes, they were more frequent in the hypertensive group than in the normotensive (44.4 vs 24.5%, P<0.03), so the 482 Ser PGC-1 allele was in our population a risk factor for hypertension independently of WHR, homeostasis model assessment of insulin resistance, BMI and Pro12 Ala PPARgamma variant (odds ratio=4.0, 95% confidence interval 1.5-10.6, P<0.01). Multiple regression analysis showed that age- and sex-adjusted systolic blood pressure correlated with the 482 Ser PGC-1 allele regardless of those covariates. In conclusion, the Gly482 Ser variant of the PGC-1alpha gene may be an independent genetic risk factor for young-onset hypertension.
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PMID:Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents. 1621 16

Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome-proliferator activated receptors (PPARs) and liver X receptors (LXRs), acting in concert with PPARgamma Coactivator 1alpha (PGC-1alpha), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia and obesity). Recently, additional partners of PGC-1alpha have moved to the forefront of metabolic research, the estrogen-related receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function.
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PMID:Nuclear receptors, mitochondria and lipid metabolism. 1840 8

Peroxisome proliferrator-activated receptor gamma coactivator-1alpha (PGC-1alpha; PPARGC1A) is a coactivator of the nuclear hormone receptor family that participates in the transcriptional programme of lipid metabolism and oxidative stress implicated in atherogenesis. Therefore, in the present study, we investigated PPARGC1A polymorphisms in the prevalence of coronary artery disease (CAD). A case-control study comprising 342 patients with CAD and 334 controls was performed in a Chinese population. Two single nucleotide polymorphisms (Gly482Ser and Thr394Thr) in the PPARGC1A gene were genotyped and compared using the polymerase chain reaction-restriction fragment length polymorphism method. The XA (GA + AA) genotype of Gly482Ser displayed a higher frequency in CAD patients than that in control subjects (P = 0.019; adjusted odds ratio = 1.53; 95% confidence interval 1.06-2.20). No significant difference in Thr394Thr genotype distribution or in Gly482Ser-Thr394Thr haplotype combinations was found between CAD patients and controls. Furthermore, we found that the significantly increased risk of CAD associated with the XA genotypes of Gly482Ser was more evident among subjects who were younger than 64 years of age, female, overweight and with hypertension. The results indicate that the PPARGC1A Gly482Ser polymorphism may contribute to the risk of CAD in the Chinese population investigated.
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PMID:Association between PPARGC1A gene polymorphisms and coronary artery disease in a Chinese population. 1856 94

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha) is a multifunctional transcriptional regulator for the pathways controlling mitochondrial biogenesis, oxidative metabolism, and glucose homeostasis. Genetic studies have suggested that Gly482Ser polymorphism of the PGC-1alpha gene is associated with a higher risk of type 2 diabetes, obesity, and hypertension. Adiponectin is an antidiabetic and antiatherogenic adipocytokine that is specifically produced by adipose tissue, and the transcription of the adiponectin gene is regulated by PPARgamma. In this study, we examined the effect of Gly482Ser polymorphism on the plasma adiponectin level in Japanese type 2 diabetics. The Gly482Ser genotype was associated with a lower plasma adiponectin level in type 2 diabetic men, but not in type 2 diabetic women. The impact of this variation on the adiponectin promoter was also assessed by a reporter gene assay, but there was no significant difference between activation by the wild type and Gly482Ser- PGC-1alpha proteins, indicating that this variation itself has no functional effect. Evaluation of the pattern of linkage disequilibrium revealed that the Gly482Ser polymorphism is located in the largest linkage disequilibrium block of the PGC-1alpha gene. Therefore the observed gender-specific association between PGC-1alpha and the plasma adiponectin level may reflect linkage disequilibrium of Gly482Ser polymorphism with other causative variations.
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PMID:PGC-1alpha Gly482Ser polymorphism is associated with the plasma adiponectin level in type 2 diabetic men. 1861 52


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