Genetic variants on rat chromosome 8 exhibit profound effects on hypertension severity and survival during nitric oxide inhibition in spontaneously hypertensive rats

American Journal of Hypertension
Angela SchulzReinhold Kreutz

Abstract

Hypertension and mortality is aggravated by nitric oxide inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) in spontaneously hypertensive rats (SHRs) but not in Munich Wistar Frömter (MWF) rats. MWF rats carry major albuminuria quantitative trait loci on rat chromosome (RNO) 6 and RNO8; susceptibility of SHRs to L-NAME is enhanced by transfer of RNO6 from MWF rats into the SHR background. Here, we tested whether the sensitivity to L-NAME in SHRs is affected by transfer of RNO8 from MWF rats in consomic SHR-8(MWF) rats. In study 1, we analyzed survival in male SHR and SHR-8(MWF) rats in response to 18 weeks of treatment with either normal drinking water (vehicle-treated) or water containing 20mg/L L-NAME. In study 2, we analyzed blood pressure and renal damage in both strains in response to 6 weeks of treatment with L-NAME compared with vehicle-treated groups. In study 1, starting after 6 weeks of treatment with L-NAME, mortality reached 90% in SHRs in contrast with the group of L-NAME treated SHR-8(MWF) rats (P < 0.0001) in which all rats survived similar to vehicle-treated rats. In study 2, L-NAME resulted in a more pronounced increase in mean arterial blood pressures in SHRs compared with SHR-8(MWF) rats (216 ± 6 vs....Continue Reading

References

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Apr 27, 2013·The Journal of Clinical Investigation·Romer A Gonzalez-VillalobosAlicia A McDonough

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Citations

Jan 26, 2016·Journal of Theoretical Biology·Samir M Abdel-Mageed, Ehab I Mohamed
Sep 30, 2016·American Journal of Physiology. Renal Physiology·Julia DolininaBengt Rippe

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