The renin angiotensin system is a key regulator of blood pressure homeostasis. Angiotensin type 1 (AT1R) and 2 receptors (AT2R) have been investigated as targets for cisplatin-induced acute kidney injury; however, their therapeutic potential remains inconclusive. This pilot study aimed to determined the effect that acute cisplatin treatment had on angiotensin II (AngII)-induced contraction in blood vessels and expression profiles of AT1R and AT2R in mouse arteries and kidneys. Male C57BL/6 mice at 18 week of age (n = 8) were treated with vehicle or bolus dose of cisplatin (12.5 mg/kg). Thoracic aorta (TA), adnominal aorta (AA), brachiocephalic arteries (BC), iliac arteries (IL) and kidneys were collected for isometric tension and immunohistochemistry analysis. Cisplatin treatment reduced IL contraction to AngII at all doses (p < 0.01, p < 0.001, p < 0.0001); however, AngII did not induce contraction in TA, AA or BC in either treatment group. Following cisplatin treatment, AT1R expression was significantly upregulated in the media of TA (p < 0.0001) and AA (p < 0.0001), and in the endothelium (p < 0.05) media (p < 0.0001) and adventitia (p < 0.01) of IL. Cisplatin treatment significantly reduced AT2R expression in the endothelium (p < 0.05) and media (p < 0.05) of TA. In renal tubules, both AT1R (p < 0.01) and AT2R (p < 0.05) were increased following cisplatin treatment. Herein, we report that cisplatin reduces AngII-mediated contraction in IL and may be explained by an absence of normal counterregulatory expression of AT1R and AT2R, indicating other factors are involved.
- MeSH
- angiotensin II * farmakologie metabolismus MeSH
- cisplatina * farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- pilotní projekty MeSH
- receptor angiotensinu typ 1 metabolismus MeSH
- receptor angiotensinu typ 2 metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Coronavirus infections are frequent viral infections in several species. As soon as the severe acute respiratory syndrome (SARS) appeared in the early 2000s, most of the research focused on pulmonary disease. However, disorders in immune response and organ dysfunctions have been documented. Elderly individuals with comorbidities exhibit worse outcomes in all the coronavirus that cause SARS. Disease severity in SARS-CoV-2 infection is related to severe inflammation and tissue injury, and effective immune response against the virus is still under analysis. ACE2 receptor expression and polymorphism, age, gender and immune genetics are factors that also play an essential role in patients' clinical features and immune responses and have been partially discussed. The present report aims to review the physiopathology of SARS-CoV-2 infection and propose new research topics to understand the complex mechanisms of viral infection and viral clearance.
- MeSH
- angiotensin konvertující enzym 2 genetika metabolismus MeSH
- biologické markery MeSH
- COVID-19 komplikace imunologie metabolismus virologie MeSH
- cytokiny metabolismus MeSH
- energetický metabolismus MeSH
- interakce hostitele a patogenu imunologie MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- náchylnost k nemoci imunologie MeSH
- podskupiny lymfocytů imunologie metabolismus MeSH
- přirozená imunita MeSH
- receptor angiotensinu typ 2 metabolismus MeSH
- replikace viru MeSH
- SARS-CoV-2 fyziologie MeSH
- syndrom uvolnění cytokinů etiologie metabolismus MeSH
- virové receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month-old male Wistar rats (12 per group) were treated for four weeks. The first group served as a control. The remaining groups were injected with a single dose of doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10 mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the blood pressure and the level of oxidative stress were enhanced along with reduced glomerular density and increased glomerular size. Captopril, olmesartan and melatonin prevented the doxorubicin-induced increase in systolic blood pressure. All four substances significantly diminished the level of oxidative burden and prevented the reduction of glomerular density and modestly prevented the increase of glomerular size. We conclude that captopril, olmesartan, melatonin and C21 exerted a similar level of renoprotective effects in doxorubicin-induced nephrotoxicity.
- MeSH
- antioxidancia terapeutické užití MeSH
- blokátory receptoru 1 pro angiotenzin II terapeutické užití MeSH
- chronická renální insuficience chemicky indukované farmakoterapie patofyziologie MeSH
- doxorubicin MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- imidazoly terapeutické užití MeSH
- inhibitory ACE terapeutické užití MeSH
- kaptopril terapeutické užití MeSH
- krysa rodu rattus MeSH
- ledvinné látky terapeutické užití MeSH
- melatonin terapeutické užití MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- receptor angiotensinu typ 2 agonisté MeSH
- tetrazoly terapeutické užití MeSH
- výsledek terapie 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
All principal candesartan cilexetil impurities and/or degradation products were synthesized and identified. The differentiation of N-1 and N-2 ethylated candesartan cilexetil derivatives was performed using 1D and 2D NMR experiments. The influence of the magnetic field on the resolution and sensitivity of NMR experiments is shown. Selective hydrolysis of these compounds then provided corresponding producrs of hydrolysis of the ethoxy group.
- Klíčová slova
- Blopress, Atacand, Amias, Ratacand,
- MeSH
- antihypertenziva MeSH
- benzimidazoly chemická syntéza MeSH
- bifenylové sloučeniny chemická syntéza MeSH
- kontaminace léku MeSH
- magnetická rezonanční spektroskopie metody MeSH
- molekulární struktura MeSH
- receptor angiotensinu typ 2 antagonisté a inhibitory chemie MeSH
- tetrazoly chemická syntéza MeSH
OBJECTIVE: The present study was performed to examine in two-kidney, one-clip (2K1C) Goldblatt hypertensive mice: first, the relative contribution of angiotensin II receptor subtypes 1A (AT(1A)) and 1B (AT(1B)); second, the role of angiotensin II type 2 (AT(2)) receptors in the development of hypertension in wild-type (AT(1A)+/+) and AT(1A) receptor knockout (AT(1A)-/-) mice; and third, the role of increased nitric oxide synthase activity in counteracting the hypertensinogenic action of angiotensin II in this model. METHODS: AT(1A)+/+ and AT(1A)-/- mice underwent clipping of one renal artery and were infused with either saline vehicle or selective AT(2) receptor agonist CGP-42112A (CGP). Blood pressure was monitored by radiotelemetry. Blood pressure responses to the nitric oxide synthase inhibitor nitro-L-arginine-methyl-ester were evaluated. RESULTS: AT(1A)+/+ mice responded to clipping by a rise in blood pressure that was not modified by CGP infusion. Clip placement caused a slight increase in blood pressure in AT(1A)-/- mice that remained significantly lower than in AT(1A)+/+ mice. Acute nitric oxide synthase inhibition caused greater increase in blood pressure in 2K1C/AT(1A)+/+ than in AT(1A)+/+ mice. CONCLUSION: The present data support the critical role of AT(1A) receptors in the development of 2K1C hypertension, whereas AT(1B) receptors play only a minor role in blood pressure regulation in this model of angiotensin II-dependent hypertension. Activation of AT(2) receptors does not play an antagonistic role in the AT(1) receptor-mediated hypertensinogenic actions of angiotensin II in this model. Finally, enhanced nitric oxide synthase activity plays a protective role by counteracting the vasoconstrictor influences of angiotensin II in 2K1C hypertensive mice.
- MeSH
- arteria renalis MeSH
- financování organizované MeSH
- hypertenze genetika patofyziologie MeSH
- ligace MeSH
- modely nemocí na zvířatech MeSH
- myši knockoutované MeSH
- myši MeSH
- receptor angiotensinu typ 1 fyziologie genetika MeSH
- receptor angiotensinu typ 2 fyziologie genetika MeSH
- renin-angiotensin systém fyziologie MeSH
- synthasa oxidu dusnatého fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
Arteriální hypertenze je svojí vysokou prevalencí velkým problémem moderní společnosti. Prevalence arteriální hypertenze v České republice je v posledních letech udávána až 30–50 % dospělé populace. Zavedením moderních léčebných postupů došlo k zásadnímu zlepšení v prognóze hypertenzních nemocných. V rámci těchto globálních trendů byla opakovaně modernizována „Doporučení pro léčbu hypertenze“, která jsou vodítkem pro správnost a efektivnost léčby. I v jejich poslední verzi je jako zcela rovnoprávná skupina antihypertenziv zařazena skupina antagonistů receptorů pro angiotenzin II (sartanů). Tyto látky jsou specifickými a selektivními blokátory angiotenzinového receptoru subtypu AT1. V době realizace této studie byli v České republice běžně používáni dva zástupci antagonistů receptoru AT1: losartan a telmisartan. Výběr sartanu přidávaného ke stávající medikaci byl zcela na rozhodnutí ošetřujícího lékaře. Telmisartanem bylo léčeno více než 96 % nemocných, proto analyzujeme pouze tyto pacienty. Do našeho sledování byli zařazeni hypertonici léčení v ambulancích praktických lékařů, internistů, kardiologů, diabetologů a endokrinologů v krajích Středočeském, Jihočeském, Plzeňském, Libereckém, Ústeckém, Olomouckém, Pardubickém, Jihomoravském a v kraji Vysočina. Efektivita léčby hypertenze byla sledována po dobu 6 měsíců a byl sledován celý zdravotně sociální dopad kvality léčby hypertenze, kterému není zatím v naší republice věnována dostatečná pozornost.
Arterial hypertension with its high prevalence is an important concern for the modern society. In the Czech Republic, over the last years, the prevalence rates of arterial hypertension are 30–50 % in the adult population. The advent of modern therapies considerably improved prognosis in hypertensive patients. In view of these global trends, the Guidelines for the treatment of hypertension that provide recommendations for adequate and effective management of the condition were repeatedly revised. The most recent version of these guidelines ranks sartans, angiotensin II receptor antagonists, as an equal option to other groups of antihypertensives. Sartans act as specific and selective AT1 angiotensin receptor blockers. At the time of the trial, two AT1 angiotensin receptor antagonists, i.e. losartan and telmisartan, were commonly used in the Czech Republic. One of these drugs was added to the existing pharmacotherapy, with the choice being left to the discretion of the attending physician. As telmisartan was prescribed to more than 96 % of hypertensive patients, only these patients were analyzed. The study subjects were hypertensive patients treated by general practitioners, internists, cardiologists, diabetologists and endocrinologists from the following administrative regions: Central Bohemia, South Bohemia, Plzeň, Liberec, Ústí nad Labem, Olomouc, Pardubice, South Moravia and Highlands. Efficacy of antihypertensive therapy was followed up for 6 months and the focus was on
- MeSH
- antihypertenziva aplikace a dávkování MeSH
- benzimidazoly terapeutické užití MeSH
- benzoáty terapeutické užití MeSH
- krevní tlak účinky záření MeSH
- kyselina močová krev MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- poměr pasu a boků MeSH
- receptor angiotensinu typ 2 antagonisté a inhibitory terapeutické užití MeSH
- tělesná hmotnost účinky léků MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- MeSH
- cerebrovaskulární poruchy farmakoterapie MeSH
- hospitalizace MeSH
- ischemická choroba srdeční farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- komplikace diabetu farmakoterapie MeSH
- lidé MeSH
- onemocnění periferních cév farmakoterapie MeSH
- příčina smrti MeSH
- ramipril aplikace a dávkování MeSH
- randomizované kontrolované studie jako téma MeSH
- receptor angiotensinu typ 2 antagonisté a inhibitory aplikace a dávkování MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- MeSH
- antihypertenziva aplikace a dávkování farmakologie MeSH
- fixní kombinace léků MeSH
- hypertenze farmakoterapie MeSH
- inhibitory ACE aplikace a dávkování MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- lidé MeSH
- ramipril aplikace a dávkování MeSH
- receptor angiotensinu typ 2 antagonisté a inhibitory MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinické zkoušky kontrolované MeSH
