A total genome scan and pharmacogenetic study were designed to search for genetic determinants of blood pressure (BP) as well as heart and kidney weights. Genome scanning was carried out in 266 F(2) intercrosses from Prague hypertensive hypertriglyceridemic rats for phenotypes of organ weights, baseline BP, BP after blockade of the renin-angiotensin system (RAS) by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide (NO) synthase by N(G)-nitro-L-arginine methyl ester. Pharmacogenetic analysis showed that, in males, BP was controlled by two loci on chromosomes 1 and 5 (Chr1, Chr5) through the SNS, and these loci showed a positive contribution for relative kidney weight (KW/BW). On the other hand, baseline BP in females was controlled by two loci on Chr3 and Chr7. The effect of these loci was not mediated by the RAS, SNS or NO system. These loci did not show any effect for KW/BW. Negatively-linked loci for KW/BW and relative heart weight (HW/BW) were identified on Chr2 in both genders. Another negatively-linked locus for KW/BW, located on Chr8 in males, affected BP through the SNS. This locus on Chr8 overlapped with a previously-reported modifier locus for polycystic kidney disease (PKD). In conclusion, this pharmacogenetic study determined two loci for BP and relative organ mass implicating sympathetic overactivity. Concordance of the identified locus for KW/BW and BP through the SNS on Chr8 with the PKD locus revealed the importance of this region for renal complications in various diseases.
- MeSH
- farmakogenetika MeSH
- fenotyp MeSH
- genotyp MeSH
- hypertenze genetika patofyziologie MeSH
- krevní tlak účinky léků genetika fyziologie MeSH
- křížení genetické MeSH
- krysa rodu Rattus MeSH
- ledviny anatomie a histologie MeSH
- Lod skóre MeSH
- lokus kvantitativního znaku genetika MeSH
- losartan farmakologie MeSH
- mikrovaskulární angina pectoris genetika patofyziologie MeSH
- modely nemocí na zvířatech MeSH
- multifaktoriální dědičnost MeSH
- NG-nitroargininmethylester farmakologie MeSH
- pentoliniumtartrát farmakologie MeSH
- polymorfismus genetický MeSH
- potkani inbrední LEW MeSH
- potkani Wistar MeSH
- savčí chromozomy genetika MeSH
- sexuální faktory MeSH
- srdce anatomie a histologie MeSH
- tělesná hmotnost genetika fyziologie MeSH
- velikost orgánu účinky léků genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- losartan MeSH
- NG-nitroargininmethylester MeSH
- pentoliniumtartrát MeSH
Quail leg buds were grafted in place of chick leg buds or chick wing buds and vice versa at stages 18 to 21 after colonization by muscle precursor cells had been completed. Motor endplate pattern in the plantaris muscle of the grafts was analyzed before hatching by means of esterase and acetylcholinesterase staining techniques. Muscle fibre types were made visual using the myosin ATPase reaction. Investigations are based on the species-specific endplate pattern of the plantaris muscle: multiply innervated fibres in the chick and focally innervated fibres in the quail. Muscle pieces isolated from the adjacent medial gastrocnemius muscle of the grafted legs were histologically examined to judge their species-specific composition. Horseradish peroxidase was injected into the plantaris muscles of both the grafted and the opposite leg as well as in the plantaris muscle of normal quail embryos, in order to be sure that the plantaris muscle of the grafts is innervated by appropriate motoneurons. This procedural design offers for the first time a possibility to test experimentally the influences of motoneurons on endplate pattern formation under conditions corresponding to those in normal ontogenesis. It is shown that such appropriate motoneurons of one species which project to the plantaris muscle of the other species dictate the endplate pattern. When the plantaris muscle is innervated by inappropriate motoneurons, the endplate pattern inherent in the muscle primordium itself becomes realized. A sequence of hierarchically acting factors is proposed to bring different results in line. According to this, the neuronally set programme has priority compared with that set in the muscle. This is true for the normal development and might generate the high neuro-muscular specificity. If under experimental conditions the neuronal programme and the peripheral programme differ, the axons and muscle fibres selectively interact with respect to their inherent characteristics and the muscle-specific programme becomes expressed. If there is a lack of a certain axon type, muscle fibres might become innervated by non-corresponding motoneurons which alter the muscle fibre type.
- MeSH
- chiméra MeSH
- končetiny MeSH
- křepelky a křepelovití MeSH
- kuřecí embryo MeSH
- motorické neurony fyziologie MeSH
- ptáci embryologie MeSH
- svaly cytologie inervace MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
Species-specific endplate distribution and fibre-type pattern were found in the plantaris muscle (PL) of the chick and quail. The PL is proposed as a model for studies of nerve-muscle interactions in chimeras.
- MeSH
- druhová specificita MeSH
- křepelky a křepelovití anatomie a histologie MeSH
- kur domácí anatomie a histologie MeSH
- nervosvalová ploténka anatomie a histologie MeSH
- nervosvalové spojení anatomie a histologie MeSH
- noha (od hlezna dolů) MeSH
- svaly anatomie a histologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH