The study of ontogenetic aspects of water and electrolyte metabolism performed in the Institute of Physiology (Czechoslovak Academy of Sciences) led to the research on the increased susceptibility of immature rats to salt-dependent forms of hypertension since 1966. Hemodynamic studies in developing rats paved the way to the evaluation of hemodynamic mechanisms during the development of genetic hypertension in SHR. A particular attention was focused on altered renal function and kidney damage in both salt and genetic hypertension with a special respect to renin-angiotensin system. Renal damage associated with hypertension progression was in the center of interest of several research groups in Prague. The alterations in ion transport, cell calcium handling and membrane structure as well as their relationship to abnormal lipid metabolism were studied in a close cooperation with laboratories in Munich, Glasgow, Montreal and Paris. The role of NO and oxidative stress in various forms of hypertension was a subject of a joint research with our Slovak colleagues focused mainly on NO-deficient hypertension elicited by chronic L-NAME administration. Finally, we adopted a method enabling us to evaluate the balance of vasoconstrictor and vasodilator mechanisms in BP maintenance. Using this method we demonstrated sympathetic hyperactivity and relative NO deficiency in rats with either salt-dependent or genetic hypertension. At the end of the first decennium of this century we were ready to modify our traditional approach towards modern trends in the research of experimental hypertension. Keywords: Salt-dependent hypertension o Genetic hypertension o Body fluids o Hemodynamics o Ion transport o Cell membrane structure and function o Renal function o Renin-angiotensin systems.

• MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Hypertension * metabolism   physiopathology   MeSH
• Blood Pressure MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Renin-Angiotensin System MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.

• MeSH
• CD36 Antigens genetics   MeSH
• Cerebrovascular Disorders genetics   physiopathology   MeSH
• Phenotype MeSH
• Genotype MeSH
• Hemodynamics genetics   MeSH
• Hypertension genetics   physiopathology   MeSH
• Insulin blood   genetics   MeSH
• Blood Glucose genetics   metabolism   MeSH
• Rats MeSH
• Lipids blood   genetics   MeSH
• Rats, Inbred BN MeSH
• Rats, Inbred SHR MeSH
• Risk Factors MeSH
• Sequence Deletion MeSH
• Cluster Analysis MeSH
• Animals, Congenic MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Names of Substances
• CD36 Antigens MeSH
• Insulin MeSH
• Blood Glucose MeSH
• Lipids MeSH

• MeSH
• Chromosomes MeSH
• Genetic Linkage * MeSH
• Rats, Inbred Strains MeSH
• Rats MeSH
• Chromosome Mapping * MeSH
• Molecular Sequence Data MeSH
• Polymerase Chain Reaction MeSH
• Polymorphism, Restriction Fragment Length MeSH
• Receptors, Retinoic Acid genetics   MeSH
• Sequence Homology, Nucleic Acid MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Names of Substances
• Receptors, Retinoic Acid MeSH
• retinoic acid binding protein I, cellular MeSH Browser

The genes that determine the baseline hematocrit level in humans and experimental animals are unknown. The spontaneously hypertensive rat (SHR), the most widely used animal model of human essential hypertension, exhibits an increased hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54 +/- 0.02 vs. 0.44 +/- 0.02, p < 0.01). Distribution of hematocrit values among recombinant inbred (RI) strains derived from SHR and BN-Lx progenitors was continuous, which suggests a polygenic mode of inheritance. The narrow heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on Chromosome (Chr) 4 showed the strongest association (p < 0.0001) with the observed variability of hematocrit among RI strains. The erythropoietin (Epo) gene, originally reported to be syntenic with Eno2, has been mapped to Chr 12, thus excluding it as a potential candidate gene for the increased hematocrit in the SHR. The current linkage data extend homologies between rat, mouse, and human chromosomes.

• MeSH
• Chromosomes MeSH
• Erythropoietin genetics   MeSH
• Genetic Linkage MeSH
• Genetic Markers MeSH
• Hematocrit * MeSH
• Rats, Inbred Strains MeSH
• Blood Pressure physiology   MeSH
• Rats MeSH
• Humans MeSH
• Chromosome Mapping methods   MeSH
• Mice MeSH
• Rats, Inbred SHR genetics   MeSH
• Recombination, Genetic MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Names of Substances
• Erythropoietin MeSH
• Genetic Markers MeSH

• MeSH
• DNA Primers MeSH
• Genetic Linkage MeSH
• Rats, Inbred Strains genetics   MeSH
• Carboxylesterase MeSH
• Carboxylic Ester Hydrolases genetics   MeSH
• Rats MeSH
• Chromosome Mapping * MeSH
• Molecular Sequence Data MeSH
• Polymerase Chain Reaction MeSH
• DNA, Satellite genetics   MeSH
• Base Sequence MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA Primers MeSH
• Carboxylesterase MeSH
• Carboxylic Ester Hydrolases MeSH
• DNA, Satellite MeSH