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
• hypertenze * patofyziologie   metabolismus   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• renin-angiotensin systém účinky léků   fyziologie   MeSH
• sympatický nervový systém patofyziologie   účinky léků   MeSH
• vazodilatace účinky léků   fyziologie   MeSH
• vazokonstrikce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The hearts of spontaneously hypertensive rats (SHR) are prone to malignant arrhythmias, mainly due to disorders of electrical coupling protein Cx43 and the extracellular matrix. Cold acclimation may induce cardio-protection, but the underlying mechanisms remain to be elucidated. We aimed to explore whether the adaptation of 9-month-old hairless SHRM to cold impacts the fundamental cardiac pro-arrhythmia factors, as well as the response to the thyroid status. There were no significant differences in the registered biometric, redox and blood lipids parameters between hairless (SHRM) and wild type SHR. Prominent findings revealed that myocardial Cx43 and its variant phosphorylated at serine 368 were increased, while an abnormal cardiomyocyte Cx43 distribution was attenuated in hairless SHRM vs. wild type SHR males and females. Moreover, the level of β-catenin, ensuring mechanoelectrical coupling, was increased as well, while extracellular matrix collagen-1 and hydroxyproline were lower and the TGF-β1 and SMAD2/3 pathway was suppressed in hairless SHRM males compared to the wild type strain. Of interest, the extracellular matrix remodeling was less pronounced in females of both hypertensive strains. There were no apparent differences in response to the hypothyroid or hyperthyroid status between SHR strains concerning the examined markers. Our findings imply that hairless SHRM benefit from cold acclimation due to the attenuation of the hypertension-induced adverse downregulation of Cx43 and upregulation of extracellular matrix proteins.

• Klíčová slova
• cardiac Cx43, cold acclimation, extracellular matrix, hairless SHRM, thyroid hormones,
• Publikační typ
• časopisecké články MeSH

Salt hypertensive Dahl rats are characterized by sympathoexcitation and relative NO deficiency. We tested the hypothesis that the increased blood pressure (BP) response to fasudil in salt hypertensive Dahl rats is due to augmented calcium sensitization in the salt-sensitive strain and/or due to their decreased baroreflex efficiency. BP reduction after acute administration of nifedipine (an L-type voltage-dependent calcium channel blocker) or fasudil (a Rho kinase inhibitor) was studied in conscious intact rats and in rats subjected to acute NO synthase inhibition or combined blockade of the renin-angiotensin system (captopril), sympathetic nervous system (pentolinium), and NO synthase (L-NAME). Intact salt-sensitive (SS) Dahl rats fed a low-salt diet had greater BP responses to nifedipine (-31 ± 6 mmHg) or fasudil (-34 ± 7 mmHg) than salt-resistant (SR) Dahl rats (-16 ± 4 and -17 ± 2 mmHg, respectively), and a high-salt intake augmented the BP response only in SS rats. These BP responses were doubled after acute NO synthase inhibition, indicating that endogenous NO attenuates both calcium entry and calcium sensitization. Additional pentolinium administration, which minimized sympathetic compensation for the drug-induced BP reduction, magnified the BP responses to nifedipine or fasudil in all groups except for salt hypertensive SS rats due to their lower baroreflex efficiency. The BP response to the calcium channel blocker nifedipine can distinguish SS and SR rats even after calcium sensitization inhibition by fasudil, which was not seen when fasudil was administered to nifedipine-pretreated rats. Thus, enhanced calcium entry (potentiated by sympathoexcitation) in salt hypertensive Dahl rats is the abnormality that is essential for their BP increase, which was further augmented by increased calcium sensitization in salt-sensitive Dahl rats.

• Klíčová slova
• Baroreflex efficiency, Fasudil, Nifedipine, Nitric oxide, Rho kinase, Sympathetic tone, Voltage-dependent calcium channels,
• MeSH
• hypertenze * farmakoterapie   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• kuchyňská sůl * MeSH
• potkani inbrední Dahl MeSH
• vápník MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kuchyňská sůl * MeSH
• vápník MeSH

It is widely accepted that sympathetic nervous system plays a crucial role in the development of hypertension. On the other hand, the role of adrenal medulla (the adrenomedullary component of the sympathoadrenal system) in the development and maintenance of high blood pressure in man as well as in experimental models of hypertension is still controversial. Spontaneously hypertensive rats (SHR) are the most widely used animal model of human essential hypertension characterized by sympathetic hyperactivity. However, the persistence of moderately elevated blood pressure in SHR subjected to sympathectomy neonatally as well as the resistance of adult SHR to the treatment by sympatholytic drugs suggests that other factors (including enhanced activity of the adrenomedullary hormonal system) are involved in the pathogenesis of hypertension of SHR. This review describes abnormalities in adrenomedullary hormonal system of SHR rats starting with the hyperactivity of brain centers regulating sympathetic outflow, through the exaggerated activation of sympathoadrenal preganglionic neurons, to the local changes in chromaffin cells of adrenal medulla. All the above alterations might contribute to the enhanced release of epinephrine and/or norepinephrine from adrenal medulla. Special attention is paid to the alterations in the expression of genes involved in catecholamine biosynthesis, storage, release, reuptake, degradation and adrenergic receptors in chromaffin cells of SHR. The contribution of the adrenomedullary hormonal system to the development and maintenance of hypertension as well as its importance during stressful conditions is also discussed.

• MeSH
• dřeň nadledvin metabolismus   patofyziologie   MeSH
• hormony metabolismus   MeSH
• hypertenze genetika   metabolismus   patofyziologie   MeSH
• krevní tlak genetika   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• potkani inbrední SHR MeSH
• sympatický nervový systém patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hormony MeSH

KEY POINTS: In mammals, the mother-offspring interaction is essential for health later in adulthood. The impact of altered timing and quality of maternal care on the offspring's circadian system was assessed using a cross-strain fostering approach. Better maternal care facilitated the development of amplitudes of Bmal1 clock gene expression in the central clock, as well as the clock-driven activity/rest rhythm, and also its entrainment to the external light/dark cycle. Worse maternal care impaired entrainment of the central clock parameters in the Wistar rat during the early developmental stages. Better maternal care remedied the dampened amplitudes of the colonic clock, as well as cardiovascular functions. The results provide compelling evidence that the circadian phenotype of a foster mother may affect the pathological symptoms of the offspring, even if they are genetically programmed. ABSTRACT: In mammals, the mother-offspring interaction is essential for health later in adulthood. Maternal care is determined by the circadian phenotype of the mother. The impact of altered timing and quality of maternal care on the circadian system was assessed using a cross-strain fostering approach, with 'abnormal' (i.e. circadian misaligned) care being represented by spontaneously hypertensive rats (SHR) and 'normal' care by Wistar rats. The SHR mothers worsened synchrony of the central clock in the suprachiasmatic nuclei with the light/dark cycle in Wistar rat pups, although this effect disappeared after weaning. The maternal care provided by Wistar rat mothers to SHR pups facilitated the development of amplitudes of the Bmal1 expression rhythm in the suprachiasmatic nuclei of the hypothalamus, as well as the clock-driven activity/rest rhythm and its entrainment to the external light/dark cycle. The peripheral clocks in the liver and colon responded robustly to cross-strain fostering; the circadian phenotype of the Wistar rat foster mother remedied the dampened amplitudes of the colonic clock in SHR pups and improved their cardiovascular functions. In general, the more intensive maternal care of the Wistar rat mothers improved most of the parameters of the abnormal SHR circadian phenotype in adulthood; conversely, the less frequent maternal care of the SHR mothers worsened these parameters in the Wistar rat during the early developmental stages. Altogether, our data provide compelling evidence that the circadian phenotype of a foster mother may positively and negatively affect the regulatory mechanisms of various physiological parameters, even if the pathological symptoms are genetically programmed.

• Klíčová slova
• circadian clock, colon, development, heart rate, liver, locomotor activity, maternal care, suprachiasmatic nucleus,
• MeSH
• chování zvířat fyziologie   MeSH
• cirkadiánní hodiny fyziologie   MeSH
• druhová specificita MeSH
• fenotyp MeSH
• mateřské chování fyziologie   MeSH
• novorozená zvířata MeSH
• nucleus suprachiasmaticus fyziologie   MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Calcium sensitization mediated by RhoA/Rho kinase pathway can be evaluated either in the absence (basal calcium sensitization) or in the presence of endogenous vasoconstrictor systems (activated calcium sensitization). Our aim was to compare basal and activated calcium sensitization in three forms of experimental hypertension with increased sympathetic tone and enhanced calcium entry-spontaneously hypertensive rats (SHR), heterozygous Ren-2 transgenic rats (TGR), and salt hypertensive Dahl rats. Activated calcium sensitization was determined as blood pressure reduction induced by acute administration of Rho kinase inhibitor fasudil in conscious rats with intact sympathetic nervous system (SNS) and renin-angiotensin system (RAS). Basal calcium sensitization was studied as fasudil-dependent difference in blood pressure response to calcium channel opener BAY K8644 in rats subjected to RAS and SNS blockade. Calcium sensitization was also estimated from reduced development of isolated artery contraction by Rho kinase inhibitor Y-27632. Activated calcium sensitization was enhanced in all three hypertensive models (due to the hyperactivity of vasoconstrictor systems). In contrast, basal calcium sensitization was reduced in SHR and TGR relative to their controls, whereas it was augmented in salt-sensitive Dahl rats relative to their salt-resistant controls. Similar differences in calcium sensitization were seen in femoral arteries of SHR and Dahl rats.

• MeSH
• geneticky modifikovaná zvířata MeSH
• hypertenze etiologie   genetika   metabolismus   patologie   MeSH
• kinázy asociované s rho antagonisté a inhibitory   genetika   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• potkani inbrední Dahl MeSH
• potkani inbrední SHR MeSH
• signální transdukce účinky léků   MeSH
• sympatický nervový systém metabolismus   patologie   MeSH
• vápník aplikace a dávkování   metabolismus   MeSH
• vazokonstrikce genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kinázy asociované s rho MeSH
• vápník MeSH