Sympathetic hyperactivity and relative NO deficiency are characteristic alterations in both genetic and salt hypertension. The contribution of these abnormalities to blood pressure (BP) maintenance can be determined in conscious rats using a consecutive blockade of particular vasoactive systems. Thus, the contribution of pressor effects of angiotensin II to the maintenance of high BP is usually small, but the role of renin-angiotensin system in the development of hypertension mediated by central and peripheral effects of angiotensin II on sympathetic activity is highly important. This is even true in angiotensin-dependent hypertension of heterozygous Ren-2 transgenic rats in which sympathetic hyperactivity is increasing with age. Central sympathoexcitation in this hypertensive model can be inhibited by lower losartan doses than peripheral angiotensin II-dependent vasoconstriction. This experimental model also yielded important knowledge on nephroprotective effects of new therapeutic drugs - endothelin receptor type A blockers. A considerable part of sympathetic vasoconstriction is dependent on the interaction of Ca2+ sensitization (RhoA/Rho kinase pathway) and Ca2+ influx (through L-VDCC). The blockade of these pathways prevents a major part of sympathetic vasoconstriction. Ca2+ sensitization seems to be attenuated in genetic hypertension in order to compensate increased Ca2+ influx. In contrast, enhanced Ca2+ sensitization is a hallmark of salt sensitivity in Dahl rats in which salt hypertension is dependent on increased Ca2+ influx. The attention should also be paid to the impairment of arterial baroreflex sensitivity which permits enhanced BP responses to pressor or depressor stimuli. Some abnormalities can be studied in blood vessels isolated from hypertensive rats but neither conduit arteries nor mesenteric resistance arteries represent the vascular beds decisive for the increased peripheral resistance and high BP. Keywords: Sympathetic vasoconstriction, NO-dependent vasodilatation, Calcium sensitization, Calcium influx, Arterial baroreflex, Spontaneously hypertensive rats, Salt hypertensive Dahl rats, Ren-2 transgenic rats, RAS blockade, SNS blockade, NOS inhibition, Endothelin, Vascular contraction and relaxation, Isolated conduit and resistance arteries, EDCF, PGI2, BKCa channels.

• MeSH
• Hypertension * physiopathology   metabolism   MeSH
• Blood Pressure physiology   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Renin-Angiotensin System physiology   MeSH
• Sympathetic Nervous System * physiopathology   metabolism   MeSH
• Vasodilation * physiology   drug effects   MeSH
• Vasoconstriction * physiology   drug effects   MeSH
• Animals MeSH
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• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

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
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• History, 20th Century MeSH
• History, 21st Century MeSH
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH

Intensive research into the presence of endogenous digitalis-like factor (EDLF) started shortly after identification of the alpha subunit of the Na,K,-ATPase as being receptor for digitalis glycosides. After years of skepticism, present data testify EDLF really exists. Most probably, the EDLF has chemical structure of either ouabain or of one of its isomers. It is secreted by the adrenal cortex, and, under conditions of stress, it's secretion is regulated differently from the secretion of both gluco- and mineralocorticoids. The physiological role of the EDLF has not been fully understood yet. In the newborn's kidneys, the inhibition of the Na,K-ATPase may assist to increase elimination of surplus sodium from the organism. In individuals of any age, the inhibitory influence of EDLF upon Na,K-ATPase in the arterial wall smooth muscle cells increases peripheral vascular resistance and thus, blood pressure. In the tissue culture, direct positive inotropic influences of EDLF upon rat cardiomyocytes was observed. However, the importance of positive inotropic effect of the EDLF upon the heart in clinical medicine remains to be elucidated.

• MeSH
• Chemical Phenomena MeSH
• Chemistry MeSH
• Digoxin * MeSH
• Enzyme Inhibitors chemistry   metabolism   MeSH
• Cardenolides MeSH
• Rats MeSH
• Humans MeSH
• Saponins chemistry   metabolism   MeSH
• Animals MeSH
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• Rats MeSH
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• digoxin-like factors MeSH Browser
• Digoxin * MeSH
• Enzyme Inhibitors MeSH
• Cardenolides MeSH
• Saponins MeSH