Publication Date:
2014-02-07
Description:
BACKGROUND 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. METHODS 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. RESULTS 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. 180±11mm Hg; P 〈 0.05). In contrast, tubulointerstitial kidney damage was even lower in SHRs compared with SHR-8 MWF rats after L-NAME treatment ( P 〈 0.05), whereas albuminuria was not different between strains. CONCLUSIONS The blood pressure increase and impaired survival of SHRs in response to nitric oxide inhibition is profoundly influenced by genes on RNO8.
Print ISSN:
0895-7061
Electronic ISSN:
1879-1905
Topics:
Medicine
Permalink
