The aim of this study was to investigate the effect of high fructose intake associated with moderate increase in adiposity on rat arterial adrenergic responses and their modulation by perivascular adipose tissue (PVAT). After eight-week-lasting substitution of drinking water with 10 % fructose solution in adult normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), their systolic blood pressure, plasma triglycerides, and relative liver weight were elevated when compared to their respective control groups. Moreover, in SHR, body weight and relative heart weight were increased after treatment with fructose. In superior mesenteric arteries, PVAT exerted inhibitory influence on adrenergic contractile responses and this effect was markedly stronger in control WKY than in SHR. In fructose-administered WKY, arterial adrenergic contractions were substantially reduced in comparison with the control group; this was caused mainly by enhancement of anticontractile action of PVAT. The diminution of the mesenteric arterial contractions was not observed after fructose treatment in SHR. We conclude that the increase in body adiposity due to fructose overfeeding in rats might have prehypertensive effect. However, in WKY it might cause PVAT-dependent and independent reduction in arterial contractile responses to adrenergic stimuli, which could attenuate the pathological elevation in vascular tone.
- MeSH
- adrenergní látky farmakologie MeSH
- arteriae mesentericae účinky léků fyziologie MeSH
- fruktosa aplikace a dávkování toxicita MeSH
- hypertenze patofyziologie MeSH
- krevní tlak účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- náhodné rozdělení MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- tuková tkáň krevní zásobení účinky léků fyziologie MeSH
- vazokonstrikce účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The inhibitory action of perivascular adipose tissue (PVAT) in modulation of arterial contraction has been recently recognized and contrasted with the prohypertensive effect of obesity in humans. In this study we demonstrated that PVAT might have opposing effect on sympatho-adrenergic contractions in different rat conduit arteries. In superior mesenteric artery isolated from normotensive Wistar-Kyoto rats (WKY), PVAT exhibited inhibitory influence on the contractions to exogenous noradrenaline as well as to endogenous noradrenaline released from arterial sympathetic nerves during transmural electrical stimulation or after application of tyramine. In contrast, the abdominal aorta with intact PVAT responded with larger contractions to transmural electrical stimulation and tyramine when compared to the aorta after removing PVAT; the responses to noradrenaline were similar in both. This indicates that PVAT may contain additional sources of endogenous noradrenaline which could be responsible for the main difference in the modulatory effect of PVAT on adrenergic contractions between abdominal aortas and superior mesenteric arteries. In spontaneously hypertensive rats (SHR), the anticontractile effect of PVAT in mesenteric arteries was reduced, and the removal of PVAT completely eliminated the difference in the dose-response curves to exogenous noradrenaline between SHR and WKY. These results suggest that in mesenteric artery isolated from SHR, the impaired anticontractile influence of PVAT might significantly contribute to its increased sensitivity to adrenergic stimuli.
- MeSH
- arterie inervace patofyziologie MeSH
- hypertenze patofyziologie MeSH
- krevní tlak * MeSH
- krysa rodu rattus MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- sympatický nervový systém patofyziologie MeSH
- tuková tkáň patofyziologie MeSH
- vazokonstrikce MeSH
- vazomotorický systém patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Peptide urotensin II was originally isolated from the urophysis of teleost fishes; later it was identified also in higher vertebrates in various organs and tissues, including cardiovascular structures. Since its discovery it has been consi- dered as a highly potent vasoconstrictor inducing contraction of smooth muscle in subnanomolar concentrations. Its wide distribution as well as its high interspecies homology indicates that this peptide is involved in regulation of many important physiological functions in vertebrates. An effort to discover other possible functions of urotensin II was intensified by the identification of its G-protein coupled receptor and its identification in humans. Furthermore, altered levels of expression of urotensin II and its receptor were found in various disease states including hypertensi- on, diabetes, heart and renal failure, in experimental animal models as well as in humans. Therefore, there is widely discussed question regarding the possible role of urotensin II in etiopathogeneses of these diseases, however the exact mechanisms are still unknown. The aim of this review is to summarize the current knowledge about urotensin II with emphasis to its direct and undirect effects in cardiovascular system.
- Klíčová slova
- urotenzín II, rozvodné artérie,
- MeSH
- aorta thoracica účinky léků MeSH
- biosyntéza peptidů * MeSH
- Haplorrhini MeSH
- kardiovaskulární fyziologické jevy MeSH
- klinické zkoušky jako téma MeSH
- krevní tlak fyziologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- ovce MeSH
- průchodnost cév účinky léků MeSH
- receptory peptidů chemie terapeutické užití MeSH
- ryby MeSH
- srdeční frekvence MeSH
- sympatický nervový systém fyziologie MeSH
- vazokonstriktory analýza terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- antihypertenziva terapeutické užití MeSH
- fenotyp MeSH
- financování organizované MeSH
- hypertenze farmakoterapie genetika prevence a kontrola MeSH
- lidé MeSH
- potkani inbrední SHR fyziologie růst a vývoj MeSH
- růst a vývoj účinky léků MeSH
- vývojová biologie trendy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
It is documented that in chronic hypertensive state there is an increased vasodepressor response to calcium channel antagonists such as the dihydropyridine derivate nifedipine. This effect is generally proportional to initial blood pressure as was demonstrated in several models of experimental hypertension. In the present study we investigated the effect of chronic nifedipine treatment on the development of cardiovascular system in young spontaneously hypertensive rats (SHR) in order to evaluate whether it could prevent the abnormalities leading to hypertensive state. Four- and eight-week-old rats were treated with nifedipine (50 mg/kg/day) for 4 weeks. Blood pressure of nifedipine-treated SHR remained at the initial level in contrast to their untreated controls where it continued to increase. In both age groups, chronic nifedipine administration reduced neurogenic contractions of isolated superior mesenteric artery, but did not significantly affect the dose-response curve to exogenous noradrenaline in 8-week-old rats. In contrast, maximum response to noradrenaline was significantly attenuated in mesenteric artery of 12-week-old nifedipine-treated SHR. We can presume that the antihypertensive effect of nifedipine is similar in both stages of spontaneous hypertension development, but the mechanisms involved might be different. It seems that chronic reduction of calcium influx during the rapid phase of pathological blood pressure increase in SHR may eliminate the effect of enhanced sympathetic tone, which may have unfavorable consequences on cardiovascular structure and function.
- MeSH
- antihypertenziva farmakologie MeSH
- arteriae mesentericae metabolismus patofyziologie účinky léků MeSH
- blokátory kalciových kanálů farmakologie MeSH
- elektrická stimulace MeSH
- financování organizované MeSH
- hypertenze farmakoterapie metabolismus patofyziologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- nifedipin farmakologie MeSH
- noradrenalin farmakologie MeSH
- potkani inbrední SHR MeSH
- potkani Wistar MeSH
- progrese nemoci MeSH
- stárnutí MeSH
- sympatický nervový systém patofyziologie účinky léků MeSH
- vápník metabolismus MeSH
- vazokonstrikce účinky léků MeSH
- vazokonstriktory farmakologie MeSH
- věkové faktory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
This review concerns the role of nitric oxide (NO) in the pathogenesis of different models of experimental hypertension (NO-deficient, genetic, salt-dependent), which are characterized by a wide range of etiology. Although the contribution of NO may vary between different models of hypertension, a unifying characteristic of these models is the presence of oxidative stress that participates in the maintenance of elevated arterial pressure and seems to be a common denominator underlying endothelial dysfunction in various forms of experimental hypertension. Besides the imbalance between the endothelial production of vasorelaxing and vasoconstricting compounds as well as the relative insufficiency of vasodilator systems to compensate augmented vasoconstrictor systems, there were found numerous structural and functional abnormalities in blood vessels and heart of hypertensive animals. The administration of antihypertensive drugs, antioxidants and NO donors is capable to attenuate blood pressure elevation and to improve morphological and functional changes of cardiovascular system in some but not all hypertensive models. The failure to correct spontaneous hypertension by NO donor administration reflects the fact that sympathetic overactivity plays a key role in this form of hypertension, while NO production in spontaneously hypertensive rats might be enhanced to compensate increased blood pressure. A special attention should be paid to the modulation of sympathetic nervous activity in central and peripheral nervous system. These results extend our knowledge on the control of the balance between NO and reactive oxygen species production and are likely to be a basis for the development of new approaches to the therapy of diseases associated with NO deficiency.
- MeSH
- antihypertenziva farmakologie MeSH
- antioxidancia farmakologie MeSH
- cévní endotel metabolismus patofyziologie účinky léků MeSH
- donory oxidu dusnatého farmakologie MeSH
- financování organizované MeSH
- hypertenze MeSH
- hypertriglyceridemie genetika komplikace metabolismus MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl MeSH
- modely nemocí na zvířatech MeSH
- NG-nitroargininmethylester MeSH
- oxid dusnatý metabolismus nedostatek MeSH
- oxidační stres MeSH
- potkani inbrední SHR MeSH
- potkani Wistar MeSH
- psychický stres komplikace metabolismus MeSH
- sympatický nervový systém patofyziologie MeSH
- synthasa oxidu dusnatého antagonisté a inhibitory metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
Treatment with pertussis toxin (PTX) which eliminates the activity of G(i) 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 microg/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.
- MeSH
- acetylcholin metabolismus MeSH
- adrenergní látky metabolismus MeSH
- angiotensin II metabolismus MeSH
- aorta thoracica metabolismus účinky léků MeSH
- arteria mesenterica superior metabolismus účinky léků MeSH
- arteria pulmonalis metabolismus účinky léků MeSH
- arterie metabolismus účinky léků MeSH
- cévní endotel metabolismus účinky léků MeSH
- elektrická stimulace MeSH
- hypertenze farmakoterapie metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- krevní tlak genetika účinky záření MeSH
- krysa rodu rattus MeSH
- noradrenalin metabolismus MeSH
- pertusový toxin farmakologie MeSH
- potkani inbrední SHR MeSH
- proteiny vázající GTP - alfa-podjednotky Gi-Go antagonisté a inhibitory metabolismus MeSH
- signální transdukce fyziologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endothelium-dependent relaxation of conduit arteries. The aim of this study was to investigate the effect of long-term (4 weeks) treatment of hHTG rats with three drugs which, according to their mechanism of action, may be able to modify the endothelial function: simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase), spironolactone (an antagonist of aldosterone receptors) and L-arginine (a precursor of nitric oxide formation). At the end of fourth week the systolic blood pressure in the control hHTG group was 148+/-2 mm Hg and in control normotensive Wistar group 117+/-3 mm Hg. L-arginine failed to reduce blood pressure, but simvastatin (118+/-1 mm Hg) and spironolactone (124+/-4 mm Hg) treatment significantly decreased the systolic blood pressure. In isolated phenylephrine-precontracted aortic rings from hHTG rats endothelium-dependent relaxation was diminished as compared to control Wistar rats. Of the three drugs used, only simvastatin improved acetylcholine-induced relaxation of the aorta. We conclude that both simvastatin and spironolactone reduced blood pressure but only simvastatin significantly improved endothelial dysfunction of aorta. Prominent increase in the expression of eNOS in large conduit arteries may be the pathophysiological mechanism underlying the protective effect of simvastatin in hHTG rats.
- MeSH
- acetylcholin farmakologie MeSH
- antagonisté mineralokortikoidních receptorů farmakologie terapeutické užití MeSH
- aorta účinky léků patofyziologie MeSH
- arginin farmakologie terapeutické užití MeSH
- časové faktory MeSH
- cévní endotel účinky léků enzymologie patofyziologie MeSH
- hypertriglyceridemie farmakoterapie genetika patofyziologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- noradrenalin farmakologie MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- simvastatin farmakologie terapeutické užití MeSH
- spironolakton farmakologie terapeutické užití MeSH
- statiny farmakologie terapeutické užití MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- synthasa oxidu dusnatého, typ III MeSH
- vazodilatace účinky léků MeSH
- vazodilatancia farmakologie MeSH
- vazokonstrikce účinky léků MeSH
- vazokonstriktory farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
