DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 15-F(2t)-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher levels of DNA instability and oxidative damage to biological macromolecules than the controls. The incidence of oxidized lesions in lymphocyte DNA, but not the urinary levels of 8-oxodG, correlated with exposure to benzene and triglycerides increased this damage. Oxidative damage to lipids and proteins was associated with exposure to cPAHs and the lipid peroxidation levels positively correlated with age and LDL cholesterol, and negatively with vitamin C. The carriers of at least one variant hOGG1 (Cys) allele tended to higher oxidative damage to lymphocyte DNA than those with the wild genotype, while XPD23 (Gln/Gln) homozygotes were more susceptible to the induction of DNA strand breaks. In contrast, GSTM1 null variant seemed to protect DNA integrity.
- MeSH
- Dinoprost analogs & derivatives urine MeSH
- DNA Glycosylases genetics metabolism MeSH
- DNA drug effects MeSH
- Genetic Predisposition to Disease MeSH
- Glutathione Transferase genetics MeSH
- Guanine analogs & derivatives urine MeSH
- Protein Carbonylation drug effects MeSH
- Comet Assay MeSH
- Air Pollutants, Occupational toxicity MeSH
- Humans MeSH
- Lymphocytes chemistry drug effects MeSH
- Oxidative Stress drug effects MeSH
- Lipid Peroxidation drug effects MeSH
- Polycyclic Aromatic Hydrocarbons analysis toxicity MeSH
- Polymorphism, Genetic MeSH
- DNA Damage MeSH
- Volatile Organic Compounds analysis toxicity MeSH
- Vasoconstrictor Agents urine MeSH
- Vehicle Emissions toxicity MeSH
- Xeroderma Pigmentosum Group D Protein genetics MeSH
- Air Pollution MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Our previous studies in heterozygous Ren-2 transgenic rats (TGR) have shown that early treatment with selective endothelin (ET)(A) receptor blockade is superior to nonselective ET(A/B) receptor blockade. The aim of this study was to evaluate the role of the ET system in male heterozygous TGR with established hypertension (late-onset treatment). TGR and control Hannover Sprague-Dawley (HanSD) rats were fed a high-salt diet and were treated concomitantly with the nonselective ET(A/B) receptor blocker bosentan or the selective ET(A) receptor blocker atrasentan from day 52 of age on. Survival rate was partly increased by bosentan and fully normalized with atrasentan. Bosentan transiently decreased blood pressure (BP), whereas atrasentan significantly reduced BP as early as one week after the start of the treatment. This effect persisted for the whole experimental period. Atrasentan also substantially reduced cardiac hypertrophy, proteinuria, glomerulosclerosis and left ventricle ET-1 content. Bosentan improved and atrasentan almost restored podocyte architecture and reversed changes in podocyte phenotype represented by the expression of CD 10, desmin and vimentin. Our results demonstrate that selective ET(A) receptor blockade has more favorable effects than nonselective ET(A/B) receptor blockade and, unlike observed in homozygous TGR, ET(A) receptor blockade has similar effects in heterozygous rats with established hypertension as in young animals with developing hypertension.
- MeSH
- Angiotensin II physiology MeSH
- Endothelin Receptor Antagonists MeSH
- Microscopy, Electron MeSH
- Endothelin-1 metabolism MeSH
- Financing, Organized MeSH
- Glomerulosclerosis, Focal Segmental pathology MeSH
- Animals, Genetically Modified MeSH
- Heterozygote MeSH
- Hypertension, Malignant drug therapy genetics pathology MeSH
- Immunohistochemistry MeSH
- Blood Pressure genetics drug effects MeSH
- Rats MeSH
- Kidney pathology MeSH
- Survival Rate MeSH
- Rats, Sprague-Dawley MeSH
- Proteinuria genetics MeSH
- Receptors, Endothelin MeSH
- Renin physiology genetics MeSH
- Sodium, Dietary pharmacology MeSH
- Body Weight genetics MeSH
- Organ Size genetics MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
BACKGROUND: In the present study we evaluated plasma and kidney angiotensin II (ANG II) levels in female and male Ren-2 transgenic rats (TGR) in comparison to age-matched female and male normotensive Hannover Sprague-Dawley rats. METHODS: The rats were maintained on a normal sodium (NS) diet (0.6% NaCl) or fed a high sodium (HS) diet (2% NaCl) for 4 days or were sodium depleted by administration of 40 mg furosemide per liter drinking water overnight followed by 3 days of low sodium diet (0.01% NaCl) (LS + F). ANG II levels were determined by radioimmunoassay. RESULTS: Female TGR at the age of 38 days were already hypertensive and had developed cardiac hypertrophy, whereas male TGR at this age still exhibited a normotensive phenotype. HS diet increased the blood pressure (BP) but did not alter the ANG II levels in TGR at any age. LS + F decreased the BP without significant change in ANG II concentrations in TGR. Female TGR responded to salt loading and salt depletion by more pronounced changes in BP than male TGR. CONCLUSIONS: Female TGR develop hypertension more rapidly and the salt-sensitive component of hypertension is more pronounced in female than in male TGR. Copyright 2007 S. Karger AG, Basel.
- MeSH
- Angiotensin II pharmacology blood metabolism MeSH
- Financing, Organized MeSH
- Animals, Genetically Modified MeSH
- Heterozygote MeSH
- Cardiomegaly diet therapy blood MeSH
- Blood Pressure MeSH
- Rats MeSH
- Sodium Chloride, Dietary therapeutic use MeSH
- Kidney blood supply physiopathology MeSH
- Sex Characteristics MeSH
- Rats, Sprague-Dawley MeSH
- Hypertension, Renal diet therapy blood MeSH
- Renin-Angiotensin System physiology MeSH
- Renin genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
BACKGROUND: Previous studies have implicated that normotensive rats with normal renal renin activity respond to anesthesia and surgery with greater increases in plasma and kidney angiotensin II (ANG II) concentrations than ANG II-dependent hypertensive rats with intrarenal renin depletion. In the present study, we therefore compared plasma and kidney ANG II levels in anesthetized and conscious normotensive and ANG II-dependent hypertensive rats. METHODS: Salt-replete Hannover-Sprague-Dawley rats (HanSD) served as controls. As models of ANG II-dependent hypertension we used: 1st, transgenic rats harboring the Ren-2 renin gene (TGR); 2nd, two-kidney, one-clip (2K1C) Goldblatt hypertensive rats, and, 3rd, ANG II-infused hypertensive rats. As additional model with enhanced renin-angiotensin system (RAS) activity, salt-depleted HanSD and TGR were employed. RESULTS: In anesthetized salt-repleted HanSD, plasma and kidney ANG II levels were higher than in salt-repleted TGR, ANG II-infused and 2K1C rats. Salt depletion caused marked increases in ANG II levels in HanSD but did not alter them in TGR. In contrast, in conscious animals immediately after decapitation plasma and kidney ANG II levels were similar in salt-repleted and salt-depleted TGR, in ANG II-infused rats, in the clipped kidney of 2K1C rats and in salt-depleted HanSD and in all these groups they were significantly higher than in salt-repleted HanSD. CONCLUSIONS: These findings indicate that anesthesia increases plasma and kidney ANG II levels in HanSD to a greater degree than in ANG II-dependent models of hypertension. Therefore, the results from studies employing anesthetized animals must be interpreted with caution. Copyright 2006 S. Karger AG, Basel.
- MeSH
- Anesthesia adverse effects MeSH
- Angiotensin II blood metabolism MeSH
- Decapitation metabolism MeSH
- Financing, Organized MeSH
- Stress, Physiological MeSH
- Animals, Genetically Modified MeSH
- Hypertension metabolism MeSH
- Rats MeSH
- Kidney metabolism MeSH
- Rats, Inbred Dahl MeSH
- Rats, Sprague-Dawley MeSH
- Renin genetics MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Comparative Study MeSH
