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

Hypertension is the most prevalent cardiovascular disease of the adult population and is closely associated with serious cardiovascular events. The burden of hypertension with respect to vascular and other organ damage is greater in women. These sex differences are not fully understood. The unique feature in women is their transition to menopause accompanied by profound hormonal changes that affect the vasculature that are also associated with changes of blood pressure. Results from studies of hormone replacement therapy and its effects on the cardiovascular system are controversial, and the timing of treatment after menopause seems to be important. Therefore, revealing potential sex- and sex hormone-dependent pathophysiological mechanisms of hypertension in experimental studies could provide valuable information for better treatment of hypertension and vascular impairment, especially in postmenopausal women. The experimental rat models subjected to ovariectomy mimicking menopause could be useful tools for studying the mechanisms of blood pressure regulation after menopause and during subsequent therapy.

• MeSH
• Hormone Replacement Therapy MeSH
• Hypertension * MeSH
• Cardiovascular Diseases * epidemiology   MeSH
• Blood Pressure physiology   MeSH
• Rats MeSH
• Menopause physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Activation of nuclear factor-κB (NF-κB) by increased production of reactive oxygen species (ROS) might induce transcription and expression of different antioxidant enzymes and also of nitric oxide synthase (NOS) isoforms. Thus, we aimed at studying the effect of NF-κB inhibition, caused by JSH-23 (4-methyl-N (1)-(3-phenyl-propyl)-benzene-1,2-diamine) injection, on ROS and NO generation in hereditary hypertriglyceridemic (HTG) rats. 12-week-old, male Wistar and HTG rats were treated with JSH-23 (bolus, 10 μmol, i.v.). After one week, blood pressure (BP), superoxide dismutase (SOD) activity, SOD1, endothelial NOS (eNOS), and NF-κB (p65) protein expressions were higher in the heart of HTG rats compared to control rats. On the other hand, NOS activity was decreased. In HTG rats, JSH-23 treatment increased BP and heart conjugated dienes (CD) concentration (measured as the marker of tissue oxidative damage). Concomitantly, SOD activity together with SOD1 expression was decreased, while NOS activity and eNOS protein expression were increased significantly. In conclusion, NF-κB inhibition in HTG rats led to decreased ROS degradation by SOD followed by increased oxidative damage in the heart and BP elevation. In these conditions, increased NO generation may represent rather a counterregulatory mechanism activated by ROS. Nevertheless, this mechanism was not sufficient enough to compensate BP increase in HTG rats.

• MeSH
• Gene Expression drug effects   MeSH
• Phenylenediamines pharmacology   MeSH
• Glutathione analysis   MeSH
• Hyperlipoproteinemia Type IV pathology   veterinary   MeSH
• Blood Pressure drug effects   MeSH
• Rats MeSH
• Myocardium metabolism   MeSH
• Nitric Oxide metabolism   MeSH
• Oxidative Stress drug effects   MeSH
• Rats, Wistar MeSH
• Reactive Oxygen Species metabolism   MeSH
• Heart Ventricles metabolism   MeSH
• Superoxide Dismutase genetics   metabolism   MeSH
• Nitric Oxide Synthase Type III genetics   metabolism   MeSH
• Nitric Oxide Synthase genetics   metabolism   MeSH
• Body Weight drug effects   MeSH
• Transcription Factor RelA genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine MeSH Browser
• Phenylenediamines MeSH
• Glutathione MeSH
• Nitric Oxide MeSH
• Reactive Oxygen Species MeSH
• Superoxide Dismutase MeSH
• Nitric Oxide Synthase Type III MeSH
• Nitric Oxide Synthase MeSH
• Transcription Factor RelA MeSH

Prague hypertriglyceridemic (HTG) rats represent a suitable model of metabolic syndrome. We have established the set of F(2) hybrids derived from HTG and Lewis progenitors to investigate the relationship between respective polymorphism(s) of Igf2 gene and blood pressure (BP) or other cardiovascular phenotypes. HTG rats had elevated systolic BP and plasma triglycerides but lower plasma cholesterol compared to Lewis rats of both genders. In males, there was higher mean arterial pressure, diastolic BP and relative heart weight in HTG than in Lewis rats. The results obtained in the total population of F(2) hybrids indicated strong segregation of Igf2 genotype with plasma triglycerides. There was no segregation of Igf2 genotype with any BP component except BP changes occurring after the blockade of either renin-angiotensin system (RAS) or NO synthase. When F(2) population was analyzed according to gender, male F(2) progeny homozygous for HTG Igf2 allele had significantly higher plasma triglycerides and greater BP changes after NO synthase blockade than those homozygous for Lewis allele. On the contrary, male F(2) progeny homozygous for HTG Igf2 allele had significantly lower plasma cholesterol and smaller BP changes after RAS blockade. PCR analysis of Igf2 gene by using of microsatelite D1Mgh22 has shown polymorphism between HTG and Lewis rats. Sequence analysis of cDNA revealed insertion of 14 nucleotides in HTG gene. In conclusion, polymorphism in Igf2 gene may be responsible for differences in lipid metabolism between HTG and Lewis rats. It remains to determine how these abnormalities could be involved in BP regulation by particular vasoactive systems.

• MeSH
• Genetic Linkage MeSH
• Genotype MeSH
• Hypertriglyceridemia blood   genetics   pathology   physiopathology   MeSH
• Rats, Inbred Strains MeSH
• Insulin-Like Growth Factor II genetics   MeSH
• Blood Pressure physiology   MeSH
• Crosses, Genetic MeSH
• Rats MeSH
• Kidney anatomy & histology   MeSH
• Lipids blood   MeSH
• Microsatellite Repeats MeSH
• DNA Mutational Analysis MeSH
• Rats, Inbred Lew MeSH
• Heart anatomy & histology   MeSH
• Body Weight genetics   MeSH
• Organ Size genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Insulin-Like Growth Factor II MeSH
• Lipids MeSH

Increased blood pressure (BP) in genetic hypertension is usually caused by high activity of sympathetic nervous system (SNS) which is enhanced by central angiotensin II but lowered by central nitric oxide (NO). We have therefore evaluated NO synthase (NOS) activity as well as neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) protein expression in brainstem and midbrain of adult spontaneously hypertensive rats (SHR) characterized by enhanced sympathetic vasoconstriction. We also studied possible participation of brain NO in antihypertensive effects of chronic captopril treatment of adult SHR. NOS activity was increased in midbrain of SHR compared to Wistar-Kyoto (WKY) rats. This could be ascribed to enhanced iNOS expression, whereas nNOS expression was unchanged and eNOS expression was reduced in this brain region. In contrast, no significant changes of NOS activity were found in brainstem of SHR in which nNOS and iNOS expression was unchanged, but eNOS expression was increased. Chronic captopril administration lowered BP of adult SHR mainly by attenuation of sympathetic tone, whereas the reduction of angiotensin II-dependent vasoconstriction and the decrease of residual BP (amelioration of structural remodeling of resistance vessels) were less important. This treatment did not affect significantly either NOS activity or expression of any NOS isoform in the two brain regions. Our data do not support the hypothesis that altered brain NO formation contributes to sympathetic hyperactivity and high BP of adult SHR with established hypertension.

• MeSH
• Captopril pharmacology   MeSH
• Blood Pressure drug effects   physiology   MeSH
• Rats MeSH
• Brain drug effects   enzymology   MeSH
• NG-Nitroarginine Methyl Ester pharmacology   MeSH
• Pentolinium Tartrate pharmacology   MeSH
• Rats, Inbred SHR MeSH
• Rats, Inbred WKY MeSH
• Renin-Angiotensin System drug effects   MeSH
• Sympathetic Nervous System drug effects   MeSH
• Nitric Oxide Synthase Type I metabolism   MeSH
• Nitric Oxide Synthase Type II metabolism   MeSH
• Nitric Oxide Synthase Type III metabolism   MeSH
• Nitric Oxide Synthase antagonists & inhibitors   metabolism   MeSH
• Body Weight drug effects   MeSH
• Organ Size drug effects   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
• Captopril MeSH
• NG-Nitroarginine Methyl Ester MeSH
• Pentolinium Tartrate MeSH
• Nitric Oxide Synthase Type I MeSH
• Nitric Oxide Synthase Type II MeSH
• Nitric Oxide Synthase Type III MeSH
• Nitric Oxide Synthase MeSH