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Genetic variants on rat chromosome 8 exhibit profound effects on hypertension severity and survival during nitric oxide inhibition in spontaneously hypertensive rats.
Am J Hypertens. 2014 Mar; 27(3):294-8.AJ

Abstract

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 ± 11 mm 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.

Authors+Show Affiliations

Department of Clinical Pharmacology and Toxicology, Charité Centrum für Therapieforschung, Charité-Universitätsmedizin Berlin, Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24363279

Citation

Schulz, Angela, et al. "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, vol. 27, no. 3, 2014, pp. 294-8.
Schulz A, Schütten-Faber S, Schulte L, et al. Genetic variants on rat chromosome 8 exhibit profound effects on hypertension severity and survival during nitric oxide inhibition in spontaneously hypertensive rats. Am J Hypertens. 2014;27(3):294-8.
Schulz, A., Schütten-Faber, S., Schulte, L., Unland, J., Kossmehl, P., & Kreutz, R. (2014). 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, 27(3), 294-8. https://doi.org/10.1093/ajh/hpt236
Schulz A, et al. Genetic Variants On Rat Chromosome 8 Exhibit Profound Effects On Hypertension Severity and Survival During Nitric Oxide Inhibition in Spontaneously Hypertensive Rats. Am J Hypertens. 2014;27(3):294-8. PubMed PMID: 24363279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variants on rat chromosome 8 exhibit profound effects on hypertension severity and survival during nitric oxide inhibition in spontaneously hypertensive rats. AU - Schulz,Angela, AU - Schütten-Faber,Sabrina, AU - Schulte,Leonard, AU - Unland,Johannes, AU - Kossmehl,Peter, AU - Kreutz,Reinhold, Y1 - 2013/12/21/ PY - 2013/12/24/entrez PY - 2013/12/24/pubmed PY - 2014/10/7/medline KW - albuminuria KW - blood pressure KW - genetics KW - hypertension KW - kidney KW - nitric oxide KW - survival. SP - 294 EP - 8 JF - American journal of hypertension JO - Am J Hypertens VL - 27 IS - 3 N2 - 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 ± 11 mm 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. SN - 1941-7225 UR - https://www.unboundmedicine.com/medline/citation/24363279/Genetic_variants_on_rat_chromosome_8_exhibit_profound_effects_on_hypertension_severity_and_survival_during_nitric_oxide_inhibition_in_spontaneously_hypertensive_rats_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1093/ajh/hpt236 DB - PRIME DP - Unbound Medicine ER -