This review summarizes our findings concerning the altered balance of vasoactive systems (namely sympathetic nervous system and nitric oxide) in various forms of experimental hypertension – genetic hypertension (SHR, HTG rats), salt hypertension (Dahl rats) and NO-deficient hypertension (L-NAME-treated rats). An attempt is made to define relative NO deficiency (compared to the existing level of sympathetic vasoconstriction), to describe its possible causes and to evaluate particular indicators of its extent. A special attention is paid to reactive oxygen species, their interaction with NO metabolism, cell Ca2+ handling and blood pressure regulation. Our current effort is focused on the investigation of abnormal regulation of cytosolic Ca2+ levels in smooth muscle and endothelium of hypertensive animals. Such a research should cl
arify the mechanisms by which genetic and/or environmental factors could chronically modify blood pressure level.
The influence of chronic angiotensin ATi receptor blockade by specific antibody on the development of genetic hypertension was studied in young spontaneously hypertensive rats (SHR). The immunization of 4-week-old SHR with a small part of the angiotensin ATi receptor molecule attenuated the development of hypertension in these animals. After five subcutaneous injections of the antigen both systolic and diastolic blood pressures were significantly lower (p<0.005) in immunized SHR compared to sham- immunized SHR. No effect on blood pressure was seen in immunized Wistar-Kyoto control rats. We conclude that renin-angiotensin system might be partially involved in the development of hypertension in young spontaneously hypertensive rats because it can be attenuated by a specific antibody raised against a part of the angiotensin ATi receptor.
The relationship between possible alterations in the volume or distribution of extracellular fluid and the development of salt hypertension was studied in inbred salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats. Blood pressure, cardiac and renal hypertrophy as well as body fluid volumes were determined in young and adult SS/Jr and SR/Jr rats of both sexes that were subjected to low, normal or high salt intake for various periods of time. Salt hypertension in young salt-sensitive rats fed a 4 % NaCl diet was not accompanied by any substantial intravascular or interstitial expansion as compared to salt-resistant rats that remained normotensive. There was no sex difference in the response of blood pressure or body fluids to high salt intake. Major expansion of plasma and blood volume, which was elicited by 8 % NaCl diet feeding from prepuberty, was not accompanied by a further blood pressure rise (compared to salt hypertensive SS/Jr rats fed 4 % NaCl diet). In conclusions, salt hypertension can occur in Dahl salt-sensitive rats without major salt and water retention. The degree of intravascular expansion is not directly related to blood pressure levels in salt-loaded Dahl rats. A high salt intake seems to exert its hypertensive effects in Dahl rats preferentially by influencing the balance of vasoconstrictor and vasodilator systems rather than by increasing the haemodynamically active intravascular volume.
Our study addresses selected parameters of rat erythrocyte ion transport (Na+-K+ pump, Na+-K+-2Cl- cotransport, and passive cation fluxes) after acute or chronic hypoxia exposure. We did not find any significant change of ion transport after acute hypoxia. However, chronic hypoxia could modify ion transport because the affinity of Na+-K+ pump for intracellular Na+seems to be decreased.
A set of 131 F2 hybrids, obtained from a cross between normotensive Lewis and hypertensive hypertriglyceridaemic (HTG) rats, was studied in order to assess the relationship between blood pressure, plasma triglycerides and plasma uric acid. In progenitors, the plasma levels of triglycerides and uric acid were twice as high in HTG rats than in the Lewis rats. It was observed In the F2 cohort that high mean arterial pressure (MAP) was unrelated to body weight and relative heart or kidney weights. On the other hand, there were significant correlations between MAP and plasma triglycerides (r=0.420, n=131, p<0.0001) and between MAP and plasma uric acid (r=0.325, p<0.001). Plasma triglycerides of F2 hybrids were below the midparental values, suggesting a stronger influence of normotensive Lewis alleles. In conclusion, hypertension in hypertriglyceridaemic rats strongly cosegregated with plasma triglycerides and plasma uric acid. Our results indicated a linkage between high blood pressure and several metabolic alterations characteristic for the X syndrome.
The possible association of plasma lipids (triglycerides and cholesterol) with erythrocyte Na+ content (Na+j) and/or with alterations in red cell Na+ and K+ (Rb+) transport was studied in a population of F2 hybrids obtained by crossing hypertensive Prague hereditary hypertriglyceridaemic (HTG) rats with normotensive Lewis rats. The obtained data indicated a strong cosegregation (p<0.001) of plasma triglycerides with erythrocyte Na+ content. This was the cause for the close correlation of plasma triglycerides with the Ma+-K+ pump activity (measured as ouabain-sensitive Na+ extrusion). On the contrary, there was only marginal association (p<0.05) of erythrocyte Na+ content with plasma cholesterol which was significantly (p<0.01) related to bumetanide-sensitive Rb+ uptake mediated by the Ma+-K+ cotransport system. Na+ leak (bumetanide-resistant net Na+ uptake) correlated positively with blood pressure in female but not in male F2 rats. The close association between plasma triglycerides and erythrocyte Na+ content suggests that ion transport alterations might contribute to mechanisms responsible for the cosegregation of blood pressure with plasma triglycerides in HTG x Lewis F2 hybrids.