Total genome scans of genetically segregating populations derived from spontaneously hypertensive rats (SHR) and other rat models of essential hypertension suggested a presence of quantitative trait loci (QTL) regulating blood pressure on multiple chromosomes, including chromosome 5. The objective of the current study was to test directly a hypothesis that chromosome 5 of the SHR carries a blood pressure regulatory QTL. A new congenic strain was derived by replacing a segment of chromosome 5 in the SHR/Ola between the D5Wox20 and D5Rat63 markers with the corresponding chromosome segment from the normotensive Brown Norway (BN/Crl) rat. Arterial pressures were directly monitored in conscious, unrestrained rats by radiotelemetry. The transfer of a segment of chromosome 5 from the BN strain onto the SHR genetic background was associated with a significant decrease of systolic blood pressure, that was accompanied by amelioration of renal hypertrophy. The heart rates were not significantly different in the SHR compared to SHR chromosome 5 congenic strain. The findings of the current study demonstrate that gene(s) with major effects on blood pressure and renal mass exist in the differential segment of chromosome 5 trapped within the new SHR.BN congenic strain., M. Pravenec, V. Křen, D. Křenová, V. Zídek, M. Šimáková, A. Musilová, J. Vorlíček, E. St. Lezin, T. W. Kurtz., and Obsahuje bibliografii
Metabolic syndrome and one of its manifestations, essential hypertension, is an important cause of worldwide morbidity and mortality. Morbidity and mortality associated with hypertension are caused by organ complications. Previously we revealed a decrease of blood pressure and an amelioration of cardiac fibrosis in a congenic line of spontaneously hypertensive rats (SHR), in which a short segment of chromosome 8 (encompassing only 7 genes) was exchanged for a segment of normotensive polydactylous (PD) origin. To unravel the genetic background of this phenotype we compared heart transcriptomes between SHR rat males and this chromosome 8 minimal congenic line (PD5). We found 18 differentially expressed genes, which were further analyzed using annotations from Database for Annotation, Visualization and Integrated Discovery (DAVID). Four of the differentially expressed genes (Per1, Nr4a1, Nr4a3, Kcna5) belong to circadian rhythm pathways, aldosterone synthesis and secretion, PI3K-Akt signaling pathway and potassium homeostasis. We were also able to confirm Nr4a1 2.8x-fold upregulation in PD5 on protein level using Western blotting, thus suggesting a possible role of Nr4a1 in pathogenesis of the metabolic syndrome.