recombinant inbred
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Recombinant inbred (RI) strains (Prague HXB/BXH set) represent a unique model that allows for permanent summation of genetic and physiological information as well as the study of age-dependent changes in phenotypes and/or gene regulation. This study compared blood pressure (BP) measured in adult animals of RI strains by radiotelemetry with BP values obtained in conscious rats of comparable age subjected to short-term carotid catheterization or with those obtained by direct carotid puncture under ether anesthesia (almost 20 years ago). After radiotelemetry recording, the contribution of major vasoactive systems to BP maintenance was studied by consecutive inhibition of the renin-angiotensin system (RAS), sympathetic nervous system (SNS), and nitric oxide synthase. We found highly significant interrelationships among baseline BP values obtained by radiotelemetry, carotid catheterization, or carotid puncture. This indicates considerable stability of RI strains over the course of their long existence, and confirms the reliability of BP values used for genetic studies performed in the past. Subsequent analysis of vasoactive system participation revealed the importance of SNS for the maintenance of BP, as determined by either radiotelemetry or catheterization. The BP of catheterized rats also correlated closely with acute captopril-induced BP changes, but this was not the case for rats measured by radiotelemetry. NO-dependent vasodilatation matched the BP effects of SNS and RAS in both measuring conditions. Residual BP (recorded at sodium nitroprusside-induced dilatation of resistance vessels) was also responsible for a significant portion of the BP variation in RI strains. Our study confirms the validity of RI strains for the further genetic and physiological research of hypertension.
- MeSH
- antihypertenziva farmakologie MeSH
- financování organizované MeSH
- hypertenze farmakoterapie genetika patofyziologie MeSH
- inbrední kmeny potkanů genetika MeSH
- katetrizace MeSH
- krevní tlak genetika MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- monitorování fyziologických funkcí MeSH
- potkani inbrední SHR genetika MeSH
- rekombinantní proteiny genetika MeSH
- renin-angiotensin systém fyziologie MeSH
- srdeční frekvence genetika MeSH
- sympatický nervový systém fyziologie MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- telemetrie MeSH
- velikost orgánu genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- hypertenze MeSH
- inbrední kmeny zvířat * genetika MeSH
- rekombinace genetická MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
- MeSH
- inbrední kmeny zvířat MeSH
- modely genetické MeSH
- modely nemocí na zvířatech MeSH
- rekombinace genetická MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
In the HXB and BXH recombinant inbred strains derived from the spontaneously hypertensive rat and the normotensive Brown Norway rat, we determined the strain distribution patterns of 500 genetic markers to scan the rodent genome for quantitative trait loci regulating cardiac mass and blood pressure. The markers spanned approximately 1,139 cM of the genome and were tested for correlations with left ventricular mass adjusted for body weight, and with systolic, diastolic, and mean arterial pressures. The marker for the dopamine 1A receptor (Drd1a) on chromosome 17 showed the strongest correlation with left ventricular heart weight (P = .00038, r = -0.59) and the relationship to heart weight was independent of blood pressure. The markers showing the strongest correlations with systolic, diastolic, and mean arterial pressure were D19Mit7 on chromosome 19 (P = .0012, r = .55), D2N35 on chromosome 2 (P = .0008, r = .56), and Il6 on chromosome 4 (P = .0018, r = .53), respectively. These studies demonstrate that the HXB and BXH strains can be effectively used for genome scanning studies of complex traits and have revealed several chromosome regions that may be involved in the genetic control of blood pressure and cardiac mass in the rat.
- MeSH
- hypertenze * genetika MeSH
- krevní tlak * MeSH
- krysa rodu rattus MeSH
- mapování chromozomů * MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- rekombinace genetická MeSH
- srdce * anatomie a histologie MeSH
- velikost orgánu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
Red blood cell Na+ content as well as ouabain-resistant Na+ and Rb+ (K+) transport (susceptible or resistant to inhibition by loop diuretics) were determined in spontaneously hypertensive rats (SHR) and normotensive Brown Norway (BN) rats the erythrocytes of which were incubated in either saline or Mg(2+)-sucrose medium. Elevated ouabain-resistant Na+ net uptake contrasted with slightly decreased red blood cell Na+ content in SHR compared with BN rats. Acceleration of furosemide- and bumetanide-sensitive Na+ fluxes contributed to enhanced ouabain-resistant Na+ influx into SHR erythrocytes in saline medium, whereas higher furosemide- or bumetanide-resistant Na+ efflux caused greater ouabain-resistant Na+ efflux in Mg(2+)-sucrose medium. Furosemide- and bumetanide-resistant Rb+ leaks were augmented in SHR erythrocytes. The association of the disclosed ion transport alterations with blood pressure was examined in 20 recombinant inbred strains derived from F2 SHR x BN hybrids. Ouabain-resistant Na+ uptake as well as furosemide- and bumetanide-resistant Na+ inward leaks (but not red blood cell Na+ content or furosemide- and bumetanide-sensitive Na+ net uptake) cosegregated with systolic and pulse pressures but not diastolic pressure of the recombinant inbred strains. In contrast, neither ouabain-resistant Na+ efflux nor any component of ouabain-resistant Rb+ uptake correlated positively with blood pressure of the recombinant inbred strains. Increased ouabain-resistant Na+ influx was compensated for by accelerated ouabain-sensitive Na+ extrusion because red blood cell Na+ content was not elevated in the hypertensive strains. Thus, high cell Na+ turnover rates might be related to genetic hypertension if an altered Na+ inward leak would be less effectively compensated for in tissues involved in cardiovascular regulation.
- MeSH
- analýza rozptylu MeSH
- biologický transport MeSH
- bumetanid farmakologie MeSH
- draslík farmakokinetika MeSH
- erytrocyty * metabolismus MeSH
- furosemid farmakologie MeSH
- genetické markery MeSH
- hybridizace genetická MeSH
- hypertenze * patofyziologie MeSH
- krevní tlak genetika účinky léků MeSH
- krysa rodu rattus MeSH
- ouabain farmakologie MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- rubidium farmakokinetika MeSH
- sodík * farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- alely genetika MeSH
- fenotyp genetika MeSH
- genetické markery MeSH
- hypertenze genetika MeSH
- inbrední kmeny potkanů genetika klasifikace MeSH
- krysa rodu rattus MeSH
- mapování chromozomů MeSH
- rekombinace genetická MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
