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

BACKGROUND: The activity of perivascular adipose tissue (PVAT), a specific deposit of adipose tissue surrounding blood vessels, could contribute to sex differences in vascular tone control, particularly in dyslipidemic disorders; however, the mutual associations remain unclear. This study aimed to evaluate the relationships among sex, PVAT and vascular function in Wistar and hereditary hypertriglyceridemic (HTG) rats. Vasoactive responses of the isolated thoracic aorta with preserved or removed PVAT were compared in adult male and female Wistar and HTG rats, and the roles of nitric oxide (NO), hydrogen sulfide (H2S), cyclooxygenase (COX) and inflammatory signaling in vascular function were monitored in females. RESULTS: HTG rats were hypertensive, but females less than males. Increased 2-h glycemia was observed in HTG rats regardless of sex; however, HTG females exhibited better glucose utilization than males did. Females, independent of strain, had better preserved endothelial function than males did. PVAT inhibited endothelium-dependent relaxation in all the rats except HTG females. In HTG males, pathologically increased aortic contractility was noted; however, in HTG females, the contractile responses were lower, thus approaching physiological levels despite the pro-contractile action of COX products. In HTG females, NO contributed to endothelial function to a lesser extent than it did in controls, but the presence of PVAT eliminated this difference, which corresponded with increased NO synthase activity. Although increased protein expression of several proinflammatory factors (TNFα, IL-6, iNOS, and NfκB) was confirmed in the aortic and PVAT tissue of HTG females, the protein expression of factors regulating the adhesion and infiltration of monocytes (ICAM-1 and MCP-1) was decreased in PVAT. Moreover, in HTG females, unlike in controls, H2S produced by PVAT did not inhibit endothelial relaxation, and regardless of PVAT, endogenous H2S had beneficial anticontractile effects, which were associated with increased protein expression of H2S-producing enzymes in both aortic and PVAT tissues. CONCLUSIONS: Despite increased inflammation and the pathological impact of cyclooxygenase signaling in female HTG rats, protective vasoactive mechanisms associated with milder hypertension and improved endothelial function and contractility linked to PVAT activity were triggered. Sulfide and nitroso signaling represent important compensatory vasoactive mechanisms against hypertriglyceridemia-associated metabolic disorders and may be promising therapeutic targets in prediabetic females.

• Klíčová slova
• Hereditary hypertriglyceridaemic rats, Hydrogen sulfide, Nitric oxide, Perivascular adipose tissue, Sex,
• MeSH
• aorta thoracica patofyziologie   MeSH
• cévní endotel patofyziologie   MeSH
• krysa rodu Rattus MeSH
• oxid dusnatý * metabolismus   MeSH
• potkani Wistar * MeSH
• prediabetes * patofyziologie   metabolismus   MeSH
• sexuální faktory MeSH
• signální transdukce * fyziologie   MeSH
• sulfan * metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• oxid dusnatý * MeSH
• sulfan * 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
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• hypertenze * metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• renin-angiotensin systém MeSH
• zvířata MeSH
• Check Tag
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH

The aim of this study was to evaluate the mutual relationship among perivascular adipose tissue (PVAT) and endogenous and exogenous H2S in vasoactive responses of isolated arteries from adult normotensive (Wistar) rats and hypertriglyceridemic (HTG) rats, which are a nonobese model of metabolic syndrome. In HTG rats, mild hypertension was associated with glucose intolerance, dyslipidemia, increased amount of retroperitoneal fat, increased arterial contractility, and endothelial dysfunction associated with arterial wall injury, which was accompanied by decreased nitric oxide (NO)-synthase activity, increased expression of H2S producing enzyme, and an altered oxidative state. In HTG, endogenous H2S participated in the inhibition of endothelium-dependent vasorelaxation regardless of PVAT presence; on the other hand, aortas with preserved PVAT revealed a stronger anticontractile effect mediated at least partially by H2S. Although we observed a higher vasorelaxation induced by exogenous H2S donor in HTG rats than in Wistar rats, intact PVAT subtilized this effect. We demonstrate that, in HTG rats, endogenous H2S could manifest a dual effect depending on the type of triggered signaling pathway. H2S within the arterial wall contributes to endothelial dysfunction. On the other hand, PVAT of HTG is endowed with compensatory vasoactive mechanisms, which include stronger anti-contractile action of H2S. Nevertheless, the possible negative impact of PVAT during hypertriglyceridemia on the activity of exogenous H2S donors needs to be taken into consideration.

• Klíčová slova
• H2S, HTG, Wistar, isolated artery, metabolic syndrome, perivascular adipose tissue,
• MeSH
• aorta thoracica patofyziologie   MeSH
• cévní endotel patofyziologie   MeSH
• cystathionin-gama-lyasa metabolismus   MeSH
• hypertriglyceridemie metabolismus   MeSH
• krysa rodu Rattus MeSH
• metabolický syndrom metabolismus   patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• noradrenalin farmakologie   MeSH
• oxidace-redukce MeSH
• potkani Wistar MeSH
• signální transdukce * MeSH
• superoxiddismutasa metabolismus   MeSH
• superoxidy metabolismus   MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• vazodilatace fyziologie   MeSH
• vazokonstrikce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cystathionin-gama-lyasa MeSH
• noradrenalin MeSH
• superoxiddismutasa MeSH
• superoxidy MeSH
• synthasa oxidu dusnatého, typ III MeSH