title: Connexin 50 mutation lowers blood pressure in spontaneously hypertensive rat.
abstract: We assessed the effect of the previously uncovered gap junction protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat - dominant cataract (SHR-Dca) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR-Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR-Dca compared with SHR (P<0.01 and P<0.05, respectively; repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium; with no differences in expression between strains. SHR-Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basal insulin sensitivity in muscle. There were 21 transcripts common to the sets of 303 transcripts in kidney and 487 in heart showing >1.2-fold difference in expression between SHR and SHR-Dca. Tumor necrosis factor was the most significant upstream regulator and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR-Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR-Dca strain, decreases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney.
authors: Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. oseda@lf1.cuni.cz.
authors: O
authors: O
authors: Šeda
authors: F
authors: F
authors: Liška
authors: M
authors: M
authors: Pravenec
authors: Z
authors: Z
authors: Vernerová
authors: L
authors: L
authors: Kazdová
authors: D
authors: D
authors: Křenová
authors: V
authors: V
authors: Zídek
authors: L
authors: L
authors: Šedová
authors: M
authors: M
authors: Krupková
authors: V
authors: V
authors: Křen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D017630:Connexins / Q000235:genetics* / Q000378:metabolism*; D053263:Gene Regulatory Networks / Q000502:physiology; D006321:Heart / Q000502:physiology; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D000099264:Connexin 50
chemical_list: D017630:Connexins; D000099264:Connexin 50