The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and left ventricular hypertrophy. Catecholamines play an important role in the pathogenesis of both essential hypertension in humans and in the SHR. Recently, we obtained evidence that the SHR harbors a variant in the gene for dopamine beta hydroxylase (Dbh) that is associated with reduced adrenal expression of Dbh mRNA and reduced DBH enzymatic activity which correlated negatively with blood pressure. In the current study, we used a transgenic experiment to test the hypothesis that reduced Dbh expression predisposes the SHR to hypertension and that augmentation of Dbh expression would reduce blood pressure. We derived 2 new transgenic SHR-Dbh lines expressing Dbh cDNA under control of the Brown Norway (BN) wild type promoter. We found modestly increased adrenal expression of Dbh in transgenic rats versus SHR non-transgenic controls that was associated with reduced adrenal levels of dopamine and increased plasma levels of norepinephrine and epinephrine. The observed changes in catecholamine metabolism were associated with increased blood pressure and left ventricular mass in both transgenic lines. We did not observe any consistent changes in brainstem levels of catecholamines or of mRNA levels of Dbh in the transgenic strains. Contrary to our initial expections, these findings are consistent with the possibility that genetically determined decreases in adrenal expression and activity of DBH do not represent primary determinants of increased blood pressure in the SHR model.
- MeSH
- adrenalin metabolismus MeSH
- dopamin-beta-hydroxylasa biosyntéza genetika MeSH
- dopamin metabolismus MeSH
- geneticky modifikovaná zvířata MeSH
- hypertenze genetika patofyziologie MeSH
- komplementární DNA biosyntéza genetika MeSH
- krevní tlak genetika MeSH
- krysa rodu rattus MeSH
- mozkový kmen metabolismus MeSH
- nadledviny enzymologie MeSH
- noradrenalin metabolismus MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- regulace genové exprese enzymů genetika MeSH
- transgeny MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- skupinqa steroidů C19,
- MeSH
- anabolika aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- androgeny fyziologie klasifikace MeSH
- androstendion metabolismus škodlivé účinky terapeutické užití MeSH
- dihydrotestosteron aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- endokrinologie * metody trendy MeSH
- financování organizované metody využití MeSH
- gonády enzymologie patofyziologie patologie MeSH
- lidé MeSH
- nadledviny enzymologie patofyziologie patologie MeSH
- pohlavní hormony * izolace a purifikace metabolismus MeSH
- statistika jako téma MeSH
- steroidy * klasifikace metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- cholesterol izolace a purifikace metabolismus MeSH
- cytokiny izolace a purifikace metabolismus MeSH
- financování organizované MeSH
- granulocyty cytologie enzymologie MeSH
- hydrokortison biosyntéza metabolismus nedostatek MeSH
- hypolipoproteinemie diagnóza enzymologie metabolismus MeSH
- lidé MeSH
- nadledviny enzymologie MeSH
- polytrauma diagnóza enzymologie klasifikace MeSH
- prospektivní studie MeSH
- statistika jako téma MeSH
- steroly biosyntéza metabolismus MeSH
- syndrom systémové zánětlivé reakce diagnóza enzymologie MeSH
- Check Tag
- lidé MeSH
The localization of the activities of some selected phosphatases, peptidases and dehydrogenases were studied in cryostat sections of the developing anlage of the suprarenal gland of human embryos from 8 to 20 weeks of the intra-uterine life. In the youngest fetuses under our notice (weeks 8-12), the activity of alkaline phosphatase (AP) on the cellular membranes of the fetal cortex was very low. In contrast, the activity of acid phosphatase (AcP) was comparatively high. Peak activity was found in the cells of the central zone of the fetal cortex. Compared to the activity of the latter, the activity of non-specific esterase (ANE) was somewhat lower. Both its localization and the gradient were identical with those of acid phosphatase. Of the peptidases studied, only dipeptidyl peptidase IV (DPP IV) exhibited slight activity in deeper layers of the primitive fetal cortex after week 8. The other peptidases exhibited only traces of activity. As early as in the first stages followed, the activity of glycero-3-phosphate-dehydrogenase (alpha-GPDH) was very high in all cells of the differentiating fetal cortex. The intensity of the activity of succinate dehydrogenase (SDH) was markedly lower. In older fetuses (weeks 13-20) there was a gradual increase in the activities of most enzymes, seen, after week 15 of the intrauterine life, also in the cells of the so-called definitive cortex. Most pronounced were the increases in the activities of acid phosphatase and non-specific esterase. The relatively low activities of the enzymes under study point to a relatively low degree of cell differentiation of both the primitive and, after week 15, the definitive cortex. Pronounced morphological and functional changes occur after the 20th week of the intrauterine life.
- MeSH
- gestační stáří MeSH
- histocytochemie MeSH
- hydrolasy metabolismus MeSH
- lidé MeSH
- nadledviny embryologie enzymologie MeSH
- oxidoreduktasy metabolismus MeSH
- plod enzymologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- hormony biosyntéza sekrece MeSH
- krysa rodu rattus MeSH
- nadledviny cytologie enzymologie MeSH
- Check Tag
- krysa rodu rattus MeSH
- MeSH
- 17-hydroxykortikosteroidy biosyntéza MeSH
- androstany metabolismus MeSH
- chromatografie na tenké vrstvě MeSH
- extraembryonální obaly enzymologie MeSH
- hydroxysteroidní dehydrogenasy metabolismus MeSH
- izotopy uhlíku MeSH
- krystalizace MeSH
- lidé MeSH
- nadledviny embryologie enzymologie MeSH
- ovarium embryologie enzymologie MeSH
- papírová chromatografie MeSH
- plod metabolismus MeSH
- steroly biosyntéza MeSH
- těhotenství MeSH
- testis embryologie enzymologie MeSH
- testosteron biosyntéza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
