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12. Gender-specific genetic determinants of blood pressure and organ weight: pharmacogenetic approach

Creator:
Ueno, T., Tremblay, J., Jaroslav Kuneš, Josef Zicha, Zdena Dobešová, Pausova, Z., Deng, A. Y., Sun, Y., Jacob, H. J., and Pavel Hamet
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print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, hypertenze, farmakogenetika, hypertension, pharmacogenetics, Prague hypertriglyceridemic rat, quantitative trait locus, heart weight, kidney weight, 14, and 612
Language:
English
Description:
A total genome scan and pharmacogenetic study were designed to search for genetic determinants of blood pressure (BP) as well as heart and kidney weights. Genome scanning was carried out in 266 F2 intercrosses from Prague hypertensive hypertriglyceridemic rats for phenotypes of organ weights, baseline BP, BP after blockade of the renin-angiotensin system (RAS) by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester. Pharmacogenetic analysis showed that, in males, BP was controlled by two loci on chromosomes 1 and 5 (Chr1, Chr5) through the SNS, and these loci showed a positive contribution for relative kidney weight (KW/BW). On the other hand, baseline BP in females was controlled by two loci on Chr3 and Chr7. The effect of these loci was not mediated by the RAS, SNS or NO system. These loci did not show any effect for KW/BW. Negatively-linked loci for KW/BW and relative heart weight (HW/BW) were identified on Chr2 in both genders. Another negatively-linked locus for KW/BW, located on Chr8 in males, affected BP through the SNS. This locus on Chr8 overlapped with a previously-reported modifier locus for polycystic kidney disease (PKD). In conclusion, this pharmacogenetic study determined two loci for BP and relative organ mass implicating sympathetic overactivity. Concordance of the identified locus for KW/BW and BP through the SNS on Chr8 with the PKD locus revealed the importance of this region for renal complications in various diseases., T. Ueno, J. Tremblay, J. Kuneš, J. Zicha, Z. Dobešová, Z. Pausová, A. Y. Deng, Y. Sun, H. J. Jacob, P. Hamet., and Obsahuje bibliografii
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

13. Human genome evolution and development of cardiovascular risk factors through natural selection

Creator:
Rudolf Poledne and Josef Zicha
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Type:
model:article and TEXT
Subject:
fyziologie člověka, human physiology, Hypertension, Sodium conservation, Natural selection, Macrophages/monocytes, Inflammation, Atherosclerosis, Non-HDL cholesterol, Membrane receptors, Renal sodium handling, Cardiovascular risk factors, Urbanization, Migration, Adaptive and maladaptive traits, 14, and 612
Language:
English
Description:
Impressive advances in molecular genetic techniques allow to analyze the effects of natural selection on the development of human genome. For example, the trend towards blonde hair and blue eyes was documented. The approach to analyze possible effects of natural selection on the evolution of recent phenotypes with high risk of cardiovascular disease has not been described yet. A possible effect on the evolution of two main risk factors - hypercholesterolemia and hypertension - is presented. The close relationship of non-HDL cholesterol blood concentration to the proportion of pro-inflammatory macrophages in human visceral adipose tissue might be a result of long-lasting natural selection. Individuals with higher proportion of this phenotype might also display a higher ability to fight infection, which was very common in human setting from prehistory until Middle Ages. Successful battle against infections increased the probability to survive till reproductive age. Similar hypothesis was proposed to explain frequent hypertension in African Americans. A long-lasting selection for higher ability to conserve sodium during long-term adaptation to low sodium intake and hot weather was followed by a short-term (but very hard) natural selection of individuals during transatlantic slave transport. Only those with very high capability to retain sodium were able to survive. Natural selection of phenotypes with high plasma cholesterol concentration and/or high blood pressure is recently potentiated by high-fat high-sodium diet and overnutrition. This hypothesis is also supported by the advantage of familial hypercholesterolemia in the 19th century (at the time of high infection disease mortality) in contrast to the disadvantage of familial hypercholesterolemia during the actual period of high cardiovascular disease mortality., R. Poledne, J. Zicha., and Seznam literatury
Rights:
http://creativecommons.org/publicdomain/mark/1.0/ and policy:public

14. Impaired control of L-type voltage-dependent calcium channels in experimental hypertension

Creator:
Mária Pintérová, Silvia Líšková, Zdena Dobešová, Behuliak, M., Jaroslav Kuneš, and Josef Zicha
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie, krevní tlak, human physiology, blood pressure, L-type voltage-dependent calcium channels, calcium-activated K+ and Cl- channels, vasoactive systems, EDCF (endothelium-derived contracting factor), isolated arteries, 14, and 612
Language:
English
Description:
Blood pressure (BP) level results from the balance of vasoconstrictors (mainly sympathetic nervous system) and vasodilators (predominantly nitric oxide and endothelium-derived hyperpolarizing factor). Most of the forms of experimental hypertension are associated with sympathetic hyperactivity and endothelial dysfunction. It is evident that nitric oxide and norepinephrine are antagonists in the control of calcium influx through L-type voltage-dependent calcium channels (L-VDCC). Their effects on L-VDCC are mediated by cGMP and cAMP, respectively. Nevertheless, it remains to determine whether these cyclic nucleotides have direct effects on L-VDCC or they act through a modulation of calcium-activated K+ and Cl- channels which influence membrane potential. Rats with genetic or salt hypertension are characterized by a relative (but not absolute) NO deficiency compared to the absolute enhancement of sympathetic vasoconstriction. This dysbalance of vasoconstrictor and vasodilator systems in hypertensive animals is reflected by greater calcium influx through L-VDCC susceptible to the inhibition by nifedipine. However, when the modulatory influence of cyclic nucleotides is largely attenuated by simultaneous ganglionic blockade and NO synthase inhibition, BP of spontaneously hypertensive rats remains still elevated compared to normotensive rats due to augmented nifedipine-sensitive BP component. It remains to determine why calcium influx through L-VDCC of hypertensive rats is augmented even in the absence of modulatory influence of major vasoactive systems (sympathetic nervous system, nitric oxide)., M. Pintérová ... [et al.]., and Obsahuje seznam literatury
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

15. Inactivation of Gi proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats

Creator:
Zemančíková, A., Török, J., Josef Zicha, and Jaroslav Kuneš
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print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie, hypertenze, tepny, physiology, hypertension, arteries, pertussis toxin, adrenergic contractions, conduit arteries, angiotensin II, Gi proteins, 14, and 612
Language:
English
Description:
Treatment with pertussis toxin (PTX) which eliminates the activity of Gi proteins effectively reduces blood pressure (BP) and vascular resistance in spontaneously hypertensive rats (SHR). In this study we have compared the functional characteristics of isolated arteries from SHR with and without PTX-treatment (10 μg/kg i.v., 48 h before the experiment). Rings of thoracic aorta, superior mesenteric artery and main pulmonary artery were studied under isometric conditions to measure the reactivity of these vessels to receptor agonists and to transmural electrical stimuli. We have found that the treatment of SHR with PTX had no effect on endothelium-dependent relaxation of thoracic aorta induced by acetylcholine. In PTX-treated SHR, the maximum contraction of mesenteric artery to exogenous noradrenaline was reduced and the dose-response curve to cumulative concentration of noradrenaline was shifted to the right. Similarly, a reduction in the magnitude of neurogenic contractions elicited by electrical stimulation of perivascular nerves was observed in the mesenteric artery from PTX-treated SHR. PTX treatment of SHR also abolished the potentiating effect of angiotensin II on neurogenic contractions of the main pulmonary artery. These results indicate that PTX treatment markedly diminishes the effectiveness of adrenergic stimuli in vasculature of SHR. This could importantly affect BP regulation in genetic hypertension., A. Zemančíková, J. Török, J. Zicha, J. Kuneš., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

16. Influence of active immunization against angiotensin AT1 or AT2 receptor on hypertension development in young and adult SHR

Creator:
Blanka Železná, Leopold Veselský, Jiří Velek, Zdena Dobešová, Josef Zicha, and Jaroslav Kuneš
Format:
print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, krevní tlak, hypertrofie srdce, blood pressure, heart hypertrophy, spontaneously hypertensive rats, active immunization, angiotensin AT1 receptor, angiotensin AT2 receptor, kidney weight, 14, and 612
Language:
English
Description:
B. Železná, L. Veselský, J. Velek, Z. Dobešová, J. Zicha, J. Kuneš. and Obsahuje bibliografii
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

17. Influence of pertussis toxin pretreatment on the development of L-NAME-induced hypertension

Creator:
Josef Zicha, Jaroslav Kuneš, Vranková, S., Lýdia Jendeková, Zdena Dobešová, Mária Pintérová, and Oľga Pecháňová
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie, sympatický nervový systém, oxid dusnatý, krevní tlak, physiology, sympathetic nervous system, nitric oxide, blood pressure, inhibitory G proteins, 14, and 612
Language:
English
Description:
High blood pressure (BP) of L-NAME hypertensive rats is maintained not only by the absence of nitric oxide (NO)-dependent vasodilatation but also by the enhancement of both sympathetic and angiotensin II-dependent vasoconstriction. The aim of the present study was to evaluate the role of inhibitory G (Gi) proteins, which are involv ed in tonic sympathetic vasoconstriction, in the pathogenesis of NO-deficient hypertension. We therefore studied BP response to chronic L-NAME administration (60 mg/kg/day for 4 weeks) in rats in which the in vivo inactivation of Gi proteins was induced by injection of pertussis toxin (PTX, 10 μg/kg i.v.). The impairment of sympathetic vasoconstriction due to PTX-induced Gi protein inactivation prevents the full development of NO-deficient hypertension because BP of PTX-treated rats subjected to chronic L-NAME administration did not reach hypertensive values. Nevertheless, chronic NO synthase inhibition per se is capable to increase moderately BP even in PTX-treated rats. Our data suggest that the sympathetic vasoconstriction is essential for the development of established NO-deficient hypertension., J. Zicha ... [et al.]., and Obsahuje seznam literatury
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

18. Involvement of BKCa and KV potassium channels in cAMP-induced vasodilatation: their insufficient function in genetic hypertension

Creator:
Mária Pintérová, Behuliak, M., Jaroslav Kuneš, and Josef Zicha
Format:
print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, hypertenze, hypertension, isoprenaline, cyclic AMP, potassium channels, genetic hypertension, calcium channels, 14, and 612
Language:
English
Description:
Spontaneously hypertensive rats (SHR) are characterized by enhanced sympathetic vasoconstriction, whereas their vasodilator mechanisms are relatively attenuated compared to their high BP. The objective of our in vivo study was to evaluate whether the impaired function of BKCa and/or KV channels is responsible for abnormal cAMP-induced vasodilatation in genetic hypertension. Using conscious SHR and normotensive WKY rats we have shown that under the basal conditions cAMP overproduction elicited by the infusion of β-adrenoceptor agonist (isoprenaline) caused a more pronounced decrease of baseline blood pressure (BP) in SHR compared to WKY rats. Isoprenaline infusion prevented BP rises induced by acute NO synthase blockade in both strains and it also completely abolished the fully developed BP response to NO synthase blockade. These cAMP-induced vasodilator effects were diminished by the inhibition of either BKCa or KV channels in SHR but simultaneous blockade of both K+ channel types was necessary in WKY rats. Under basal conditions, the vasodilator action of both K+ channels was enhanced in SHR compared to WKY rats. However, the overall contribution of K+ channels to cAMP-induced vasodilator mechanisms is insufficient in genetic hypertension since a concurrent activation of both K+ channels by cAMP overproduction is necessary for the prevention of BP rise elicited by acute NO/cGMP deficiency in SHR. This might be caused by less effective activation of these K+ channels by cAMP in SHR. In conclusion, K+ channels seem to have higher activity in SHR, but their vasodilator action cannot match sufficiently the augmented vasoconstriction in this hypertensive strain., M. Pintérová, M. Behuliak, J. Kuneš, J. Zicha., and Obsahuje bibliografii
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

20. Late blood pressure reduction in SHR subjected to transient captopril treatment in youth: possible mechanisms

Creator:
Josef Zicha, Zdena Dobešová, and Jiří Kuneš
Format:
print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie, genetika živočichů, hypertenze, physiology, animal genetics, hypertension, genetic hypertension, late effects of early treatment, captopril, nifedipine, 14, and 612
Language:
English
Description:
Spontaneously hypertensive rats (SHR) are characterized by enhanced nifedipine-sensitive component of sympathetic vasoconstriction. Our study tried to elucidate the mechanisms responsible for long-term reduction of blood pressure (BP) in SHR subjected to early transient captopril treatment. Adult untreated SHR aged 30-34 weeks were compared with animals subjected to chronic captopril treatment for 6 weeks either in youth (between 4 and 10 weeks of age) or in adulthood (between 24 and 30 weeks of age). Antihypertensive effects of captopril were more pronounced in young than adult SHR. This was due to greater attenuation of sympathetic and nifedipine-sensitive BP components and prevention of residual BP rise in young captopril-treated SHR in which the reductions of nifedipine-sensitive BP component and residual BP persisted for 20 weeks after captopril withdrawal. The magnitude of nifedipine-sensitive component of sympathetic vasoconstriction is decisive for BP maintenance not only in untreated SHR but also in SHR during active captopril treatment by or after its withdrawal., J. Zicha, Z. Dobešová,J. Kuneš., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public