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
