Direct Ink Writing of Low-Concentration MXene/Aramid Nanofiber Inks for Tunable Electromagnetic Shielding and Infrared Anticounterfeiting Applications.

MXene inks offer a promising avenue for the scalable production and customization of printing electronics. However, simultaneously achieving a low solid content and printability of MXene inks, as well as mechanical flexibility and environmental stability of printed objects, remains a challenge. In this study, we overcame these challenges by employing high-viscosity aramid nanofibers (ANFs) to optimize the rheology of low-concentration MXene inks. The abundant entangled networks and hydrogen bonds formed between MXene and ANF significantly increase the viscosity and yield stress up to 103 Pa·s and 200 Pa, respectively. This optimization allows the use of MXene/ANF (MA) inks at low concentrations in direct ink writing and other high-viscosity processing techniques. The printable MXene/ANF inks with a high conductivity of 883.5 S/cm were used to print shields with customized structures, achieving a tunable electromagnetic interference shielding effectiveness (EMI SE) in the 0.2-48.2 dB range. Furthermore, the MA inks exhibited adjustable infrared (IR) emissivity by changing the ANF ratio combined with printing design, demonstrating the application for infrared anticounterfeiting. Notably, the printed MXene/ANF objects possess outstanding mechanical flexibility and environmental stability, which are attributed to the reinforcement and protection of ANF. Therefore, these findings have significant practical implications as versatile MXene/ANF inks can be used for customizable, scalable, and cost-effective production of flexible printed electronics.

Effects of high-intensity interval training on obese college students / Efeitos do treinamento intervalado de alta intensidade em universitários obesos / Efectos del entrenamiento por intervalos de alta intensidad en estudiantes universitarios obesos

ABSTRACT Introduction: Sports are a great promoter of health and high-intensity interval training (HIIT), as an aerobic activity, has great potential to promote lipid improvement in obese college students. Objective: This study aimed to develop research on HIIT-based protocols controlling body mass index and blood pressure in obese college students. Methods: Compared with traditional medium-intensity continuous training (MCT), the focus of the research has the characteristics of a relatively short time, fast effect, and high interest among participating volunteers. Results: Many studies have suggested that this program effectively controls weight and blood pressure in obese college students. Some studies have even proven that its effect is better than that of MCT. Conclusion: The long-term effect of HIIT requires further research to be verified, and its standardization and safety also need further scientific support. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: É constatado que os esportes são grandes promotores de saúde e o treinamento intervalado de alta intensidade (HIIT), como uma atividade aeróbica, tem grande potencial na promoção de melhora lipídica em universitários obesos. Objetivo: Elaborar uma pesquisa dos protocolos baseados em HIIT controlando o índice de massa corporal e a pressão sanguínea de universitários obesos. Métodos: Em comparação com o tradicional treinamento contínuo de média intensidade (MCT), o foco da pesquisa tem as características de tempo relativamente curtas, efeito rápido e alto interesse entre os voluntários participantes. Resultados: Um grande número de estudos sugeriu que este programa é eficaz no controle do peso e pressão sanguínea de universitários obesos. Alguns estudos até provaram que seu efeito é melhor do que o do MCT. Conclusão: O efeito a longo prazo do HIIT exige maiores pesquisas para ser verificado, a sua padronização e segurança também necessitam de maiores embasamentos científicos. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Se sabe que el deporte es un gran promotor de la salud y el entrenamiento por intervalos de alta intensidad (HIIT), como una actividad aeróbica, tiene un gran potencial para promover la mejora lipídica en estudiantes universitarios obesos. Objetivo: Desarrollar una investigación sobre protocolos basados en HIIT que controlen el índice de masa corporal y la presión arterial en estudiantes universitarios obesos. Métodos: En comparación con el entrenamiento continuo de intensidad media tradicional (MCT), el enfoque de la investigación tiene las características de tiempo relativamente corto, efecto rápido y alto interés entre los voluntarios participantes. Resultados: Un gran número de estudios ha sugerido que este programa es eficaz para controlar el peso y la presión arterial en estudiantes universitarios obesos. Algunos estudios han demostrado incluso que su efecto es mejor que el del MCT. Conclusión: El efecto a largo plazo del HIIT requiere más investigación para ser verificado, su estandarización y seguridad también necesitan más base científica. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone.

In rats with salt-induced hypertension or postmyocardial infarction, angiotensin II type 1 receptor (AT(1)R) densities and oxidative stress increase and neuronal NO synthase (nNOS) levels decrease in the paraventricular nucleus (PVN). The present study was designed to determine whether these changes may depend on activation of the aldosterone -'ouabain' neuromodulatory pathway. After intracerebroventricular (i.c.v.) infusion of aldosterone (20 ng h(-1)) for 14 days, blood pressure (BP) and heart rate (HR) were recorded in conscious Wistar rats, and mRNA and protein for nNOS, endothelial NO synthase (eNOS), AT(1)R and NADPH oxidase subunits were assessed in brain tissue. Blood pressure and HR were significantly increased by aldosterone. Aldosterone significantly increased mRNA and protein of AT(1)R, P22phox, P47phox, P67phox and Nox2, and decreased nNOS but not eNOS mRNA and protein in the PVN, as well as increased the angiotensin-converting enzyme and AT(1)R binding densities in the PVN and supraoptic nucleus. The increases in BP and HR, as well as the changes in mRNA, proteins and angiotensin-converting enzyme and AT(1)R binding densities were all largely prevented by concomitant i.c.v. infusion of Digibind (to bind 'ouabain') or benzamil (to block presumed epithelial sodium channels). These data indicate that aldosterone, via 'ouabain', increases in the PVN angiotensin-converting enzyme, AT(1)R and oxidative stress, but decreases nNOS, and suggest that endogenous aldosterone may cause the similar pattern of changes observed in salt-sensitive hypertension and heart failure postmyocardial infarction.

Chronic central versus systemic blockade of AT(1) receptors and cardiac dysfunction in rats post-myocardial infarction.

In rats, both central and systemic ANG II type 1 (AT(1)) receptor blockade attenuate sympathetic hyperactivity, but central blockade more effectively attenuates left ventricular (LV) dysfunction post-myocardial infarction (MI). In protocol I, we examined whether functional effects on cardiac load may play a role and different cardiac effects disappear after withdrawal of the blockade. Wistar rats were infused for 4 wk post-MI intracerebroventricularly (1 mg.kg(-1).day(-1)) or injected subcutaneously daily (100 mg x kg(-1) x day(-1)) with losartan. LV dimensions and function were assessed at 4 wk and at 6 wk post-MI, i.e., 2 wk after discontinuing treatments. At 4 and 6 wk post-MI, LV dimensions were increased and ejection fraction was decreased. Intracerebroventricular but not subcutaneous losartan significantly improved these parameters. At 6 wk, LV peak systolic pressure (LVPSP) and maximal or minimal first derivative of change in pressure over time (dP/dt(max/min)) were decreased and LV end-diastolic pressure (LVEDP) was increased. All four indexes were improved by previous intracerebroventricular losartan, whereas subcutaneous losartan improved LVEDP only. In protocol II, we evaluated effects of oral instead of subcutaneous administration of losartan for 4 wk post-MI. Losartan ( approximately 200 mg x kg(-1) x day(-1)) either via drinking water or by gavage similarly decreased AT(1) receptor binding densities in brain nuclei and improved LVEDP but further decreased LVPSP and dP/dt(max). These results indicate that effects on cardiac load by peripheral AT(1) receptor blockade or the pharmacokinetic profile of subcutaneous versus oral dosing do not contribute to the different cardiac effects of central versus systemic AT(1) receptor blockade post-MI.

Central infusion of aldosterone synthase inhibitor attenuates left ventricular dysfunction and remodelling in rats after myocardial infarction.

AIMS: Blockade of mineralocorticoid receptors in the central nervous system (CNS) prevents sympathetic hyperactivity and improves left ventricle (LV) function in rats post-myocardial infarction (MI). We examined whether aldosterone produced locally in the brain may contribute to the activation of mineralocorticoid receptors in the CNS. METHODS AND RESULTS: Two days after coronary artery ligation, Wistar rats received an intra-cerebroventricular (icv) infusion via osmotic mini-pumps of the aldosterone synthase inhibitor FAD286 at 100 microg/kg/day or vehicle for 4 weeks. LV function was assessed by echocardiography at 2 and 4 weeks, and by Millar catheter at 4 weeks. At 4 weeks post-MI, aldosterone in the hippocampus was increased by 70% and tended to increase in the hypothalamus by 20%. These increases were prevented by FAD286. Across groups, aldosterone in the hippocampus and hypothalamus showed a high correlation. There were no differences in brain corticosterone levels. Compared to sham rats, at both 2 and 4 weeks post-MI rats treated with vehicle showed increased LV dimensions and decreased LV ejection fraction. Icv infusion of FAD286 attenuated these changes in LV dimensions and ejection fraction by approximately 30%. At 4 weeks post-MI, LV peak systolic pressure (LVPSP) and dP/dt(max/min) were decreased and LV end-diastolic pressure (LVEDP) was increased. In rats treated with icv FAD286, LVPSP and dP/dt(min) remained normal and LVEDP and dP/dt(max) were markedly improved. Post-MI increases in cardiac fibrosis and cardiomyocyte diameter were substantially attenuated by icv FAD286. CONCLUSION: These data suggest that aldosterone produced locally in the brain acts as the main agonist of mineralocorticoid receptors in the CNS and contributes substantially to the progressive heart failure post MI.

Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction.

BACKGROUND: The brain renin-angiotensin system contributes significantly to progressive left ventricular (LV) dysfunction in rats after myocardial infarction (MI). The present study evaluated the effects of central versus peripheral plus central angiotensin-converting enzyme (ACE) blockade on sympathetic activity, and LV anatomy and function after MI. METHODS: Wistar rats were treated for 4 weeks after MI with the lipophilic ACE inhibitor trandolapril at 5 mg/kg/day or the hydrophilic blocker lisinopril at 50 mg/kg/day by once daily subcutaneous injection, or with a central infusion of lisinopril at 0.1 mg/kg/day. RESULTS: At 24 hours after the last dose, subcutaneous trandolapril caused 70% to 80% ACE inhibition in both brain and kidneys; lisinopril caused 10% to 20% less. Central infusion of lisinopril caused 70% inhibition of brain ACE and minimal (6%) inhibition in the kidneys. All three treatments similarly improved sympathetic reactivity and arterial baroreflex function. All three treatments lowered cardiac Ang I and II, and similarly attenuated the increases in LV end diastolic pressure, circumference, and fibrosis. Both subcutaneous treatments further decreased LV peak systolic pressure and dP/dt max, whereas icv lisinopril caused no change. CONCLUSION: Despite marked differences in the extent of peripheral blockade, all three treatments similarly affected sympathetic activity and decreased cardiac Ang II, preload and remodeling after MI. One may speculate that central and peripheral ACE-mediated mechanisms are sequential and therefore only minor additional effects of peripheral ACE blockade are noted.

Sympathetic hyperactivity and cardiac dysfunction post-MI: different impact of specific CNS versus general AT1 receptor blockade.

In rats, blockade of the brain renin-angiotensin-aldosterone system prevents sympathetic hyperactivity and markedly attenuates LV dysfunction post-MI. We evaluated whether peripheral administration of an AT(1) receptor blocker has similar effects. In the first experiment, Wistar rats were injected subcutaneously (sc) daily with losartan at a regular or high dose (15 or 100 mg/kg/day) starting 2 days post-MI. At 4 weeks, sympathetic reactivity to air stress was enhanced, baroreflex function was impaired and cardiac function clearly decreased. Increased AT(1) receptor binding densities post-MI were decreased by losartan towards (regular dose) or well below (high dose) levels of sham rats. Losartan at the high dose prevented sympathetic hyperactivity and baroreflex impairment, and lowered LVEDP but further decreased LVPSP and dP/dt(max). In the second experiment, as of 2 days post-MI, losartan (1 mg/kg/day), spironolactone (10 microg/kg/day) or vehicle was infused intracerebroventricularly (i.c.v), or losartan (100 mg/kg/day) was injected sc for 4 weeks. LV dysfunction and increased fibrosis and cardiomyocyte diameter were clearly present at 4 weeks. Icv losartan or spironolactone improved or normalized LV diastolic and systolic function, LV dimensions, fibrosis and myocyte diameter. In contrast, although sc losartan similarly improved fibrosis and LVEDP, again it did not improve LV systolic function. These data indicate that specific central and general AT(1) receptor blockade can similarly improve sympathetic hyperactivity, cardiac fibrosis and LVEDP, but only central blockade improves LV systolic function, possibly due to differences in the extent of blockade of AT(1) receptors in cardiac myocytes and/or peripheral sympathetic nerves.

Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats.

Functional studies indicate that the sympathoexcitatory and pressor responses to an increase in cerebrospinal fluid (CSF) [Na+] by central infusion of Na+-rich artificial cerebrospinal fluid (aCSF) in Wistar rats are mediated in the brain by mineralocorticoid receptor (MR) activation, ouabain-like compounds (OLC), and AT1-receptor stimulation. In the present study, we examined whether increasing CSF [Na+] by intracerebroventricular infusion of Na+-rich aCSF activates MR and thereby increases OLC and components of the renin-angiotensin system in the brain. Male Wistar rats received via osmotic minipump an intracerebroventricular infusion of aCSF or Na+-rich aCSF, in some groups combined with intracerebroventricular infusion of spironolactone (100 ng/h), antibody Fab fragments (to bind OLC), or as control gamma-globulins. After 2 wk of infusion, resting blood pressure and heart rate were recorded, OLC and aldosterone content in the hypothalamus were assessed by a specific ELISA or radioimmunoassay, and angiotensin-converting enzyme (ACE) and AT1-receptor binding densities in various brain nuclei were measured by autoradiography using 125I-labeled 351 A and 125I-labeled ANG II. When compared with intracerebroventricular aCSF, intracerebroventricular Na+-rich aCSF increased CSF [Na+] by approximately 5 mmol/l, mean arterial pressure by approximately 20 mmHg, heart rate by approximately 65 beats/min, and hypothalamic content of OLC by 50% and of aldosterone by 33%. Intracerebroventricular spironolactone did not affect CSF [Na+] but blocked the Na+-rich aCSF-induced increases in blood pressure and heart rate and OLC content. Intracerebroventricular Na+-rich aCSF increased ACE and AT1-receptor-binding densities in several brain nuclei, and Fab fragments blocked these increases. These data indicate that in Wistar rats, a chronic increase in CSF [Na+] may increase hypothalamic aldosterone and activate CNS pathways involving MR, and OLC, leading to increases in AT1-receptor and ACE densities in brain areas involved in cardiovascular regulation and hypertension.

Central and peripheral renin-angiotensin systems in ouabain-induced hypertension.

Chronic subcutaneous infusion of ouabain causes hypertension via central pathways involving angiotensin type 1 (AT(1)) receptor stimulation. The present study assessed plasma and tissue ANG I and II levels as well as AT1 receptor and angiotensin-converting enzyme (ACE) mRNA levels and binding densities by real-time PCR and in vitro autoradiography in relevant brain nuclei and peripheral tissues (heart and kidney) in rats at 1 and/or 2 wk after start of ouabain infusion at 50 microg/day. After 2 wk (but not after 1 wk), blood pressures significantly increased (+15 mmHg). At 2 wk, plasma ANG I and II levels were markedly suppressed by ouabain. In contrast, in the heart and kidneys, ANG I levels were not affected, and ANG II levels tended to decrease, whereas in the hypothalamus ANG II content clearly increased. At 1 wk, no changes in ACE and AT1 receptor densities were seen. After 2 wk, there were significant decreases in AT(1) receptor mRNA and densities in the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and paraventricular nucleus (PVN). ACE densities decreased only in the OVLT and SFO, but ACE mRNA showed more variable responses (decrease in OVLT vs. increase in PVN). In the kidneys, at 2 wk both AT1 receptor and ACE densities were decreased, but mRNA abundance did not change. The heart showed no significant changes. The increase in hypothalamic ANG II content and associated decreases in central AT1 receptor and ACE densities support the involvement of the brain renin-angiotensin system in the central hypertensive mechanism of action of ouabain.

Regulation of components of the brain and cardiac renin-angiotensin systems by 17beta-estradiol after myocardial infarction in female rats.

The present study tested the hypothesis that 17beta-estradiol (E2) inhibits increases in angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby, inhibits development of left ventricular (LV) dysfunction after MI. Age-matched female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2) ovariectomy + subcutaneous vehicle treatment (OVX + Veh), or 3) OVX + subcutaneous administration of a high dose of E2 (OVX + high-E2). After 2 wk, rats were randomly assigned to coronary artery ligation (MI) and sham operation groups and studied after 3 wk. E2 status did not affect LV function in sham rats. At 2-3 wk after MI, impairment of LV function was similar across MI groups, as measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance and activity were increased severalfold in all MI groups compared with respective sham animals and to similar levels across MI groups. In most brain nuclei, ACE and AT1R densities increased after MI. Unexpectedly, compared with the respective sham groups the relative increase was clearest (20-40%) in OVX + high-E2 MI rats, somewhat less (10-15%) in ovary-intact MI rats, and least (< 10-15%) in OVX + Veh MI rats. However, because in the sham group brain ACE and AT1R densities increased in the OVX + Veh rats and decreased in the OVX + high-E2 rats compared with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei were modestly higher (< 20%) in OVX + Veh MI rats than in the other two MI groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and amplifies the percent increases in ACE and AT1R densities in brain nuclei after MI, despite E2-induced downregulation in sham rats. Consistent with these minor variations in the tissue renin-angiotensin system, during the initial post-MI phase, E2 appears not to enhance or hinder the development of LV dysfunction.

Inhibition of brain angiotensin-converting enzyme by peripheral administration of trandolapril versus lisinopril in Wistar rats.

BACKGROUND: Peripheral administration of blockers of the renin-angiotensin system (RAS) may affect the RAS in the brain to a variable degree. In the present study, we determined inhibition of angiotensin-converting enzyme (ACE) in the brain after peripheral administration of a lipophilic (trandolapril) versus hydrophilic (lisinopril) ACE inhibitor. METHODS: Trandolapril (0.2, 1, and 5 mg/kg/day, subcutaneously) was compared with lisinopril (2, 10, and 50 mg/kg/day, subcutaneously), each for 6 days. At 4 and 24 h after the last dose, (125)I-351A binding on brain ACE was measured. RESULTS: Trandolapril and lisinopril caused similar inhibition of ligand binding outside the blood-brain barrier (BBB). However, inside the BBB, trandolapril was more effective at low and medium doses (for lisinopril, 28% to 51% inhibition at a dose of 2 mg, 63% to 72% at 10 mg, and 84% to 86% at 50 mg; and for trandolapril, 62% to 68% inhibition at a dose of 0.2 mg, 84% to 87% at 1 mg, and 88% to 93% at 5 mg). In contrast, in the brain structures caudate putamen and globus pallidus, lisinopril inhibited ligand binding better than trandolapril (for lisinopril 30% to 44% at a dose of 2 mg and 71% to 74% at 10 mg, versus for trandolapril 21% to 27% at 0.2 mg and 51% to 63% at 1 mg). At 24 h after the last dose, inhibition by trandolapril persisted more than inhibition by lisinopril both outside and inside the BBB. CONCLUSIONS: These results suggest that peripheral administration of even hydrophilic ACE inhibitors can result in marked inhibition of brain ACE inside the BBB but that different brain structures show variable inhibition.

17beta-estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats.

Estrogens have been implicated in both worsening and protecting from cardiovascular disease. The effects of 17beta-estradiol (E2) on the cardiovascular system may be mediated, at least in part, by its modulation of local tissue renin-angiotensin systems (RAS). We assessed two critical components, angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT(1)R), in the heart, lung, abdominal aorta, adrenal, kidney, and brain in four groups of female Wistar rats (n = 5-6/group): 1) sham ovariectomized, 2) ovariectomized (OVX) treated with subcutaneous vehicle, 3) OVX treated with 25 mug/day (regular) E2 subcutaneously, and 4) OVX treated with 250 mug/day (high) subcutaneous E2 for 2 or 5 wk. After 2 wk, plasma ACE activity was not altered by OVX, but it was 34-38% lower in OVX + regular E2 and OVX + high E2 rats compared with sham OVX rats, and these decreases were no longer present after 5 wk. After 5 wk, OVX alone increased ACE activity and binding densities, and AT(1)R binding densities by 15-100% in right ventricle, left ventricle (LV), kidney, lung, abdominal aorta, adrenal and several cardiovascular regulatory nuclei in the brain. These effects were, for the most part, prevented by regular E2 replacement and were reversed to decreases by high E2 treatment. This regulation of tissue ACE and AT(1)R is significant as the activity of these tissue RAS contributes to the pathogenesis and/or progression of hypertension, atherosclerosis, and LV remodeling after myocardial infarction.

Increases in brain and cardiac AT1 receptor and ACE densities after myocardial infarct in rats.

In the brain, ouabain-like compounds (OLC) and the reninangiotensin system (RAS) contribute to sympathetic hyperactivity in rats after myocardial infarction (MI). This study aimed to evaluate changes in components of the central vs. the peripheral RAS. Angiotensin-converting enzyme (ACE) and angiotensin type 1 (AT1) receptor binding densities were determined by measuring 125I-labeled 351A and 125I-labeled ANG II binding 4 and 8 wk after MI. In the brain, ACE and AT1 receptor binding increased 8-15% in the subfornical organ, 14-22% in the organum vasculosum laminae terminalis, 20-34% in the paraventricular nucleus, and 13-15% in the median preoptic nucleus. In the heart, the greatest increase in ACE and AT1 receptor binding occurred at the infarct scar (approximately 10-fold) and the least in the right ventricle (2-fold). In kidneys, ACE and AT1 receptor binding decreased 10-15%. After intracerebroventricular infusion of Fab fragments to block brain OLC from 0.5 to 4 wk after MI, increases in ACE and AT1 receptors in the subfornical organ, organum vasculosum laminae terminalis, paraventricular nucleus, and medial preoptic nucleus were markedly inhibited, and ACE and AT1 receptor densities in the heart increased less (6-fold in the infarct scar). In kidneys, decreases in ACE and AT1 receptor binding were absent after treatment with Fab fragments. These results demonstrate that ACE and AT1 receptor binding densities increase not only in the heart but also in relevant areas of the brain of rats after MI. Brain OLC appears to play a major role in activation of brain RAS in rats after MI and, to a modest degree, in activation of the cardiac RAS.

Effects of high salt intake on brain AT1 receptor densities in Dahl rats.

To assess effects of dietary salt on brain AT1 receptor densities, 4-wk-old Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats were fed a regular (101 mumol Na/g) or high (1,370 mumol Na/g)-salt diet for 1, 2, or 4 wk. AT1 receptors were assessed by quantitative in vitro autoradiography. AT1 receptor densities did not differ significantly between strains on the regular salt diet. The high-salt diet for 1 or 2 wk increased AT1 receptor binding by 21-64% in the Dahl S rats in the subfornical organ, median preoptic nucleus, paraventricular nucleus, and suprachiasmatic nucleus. No changes were noted in the Dahl R rats. After 4 wk on a high-salt diet, increases in AT1 receptor binding persisted in Dahl S rats but were now also noted in the paraventricular nucleus, median preoptic nucleus, and suprachiasmatic nucleus of Dahl R rats. At 4 wk on the diet, intracerebroventricular captopril caused clear decreases in blood pressure only in the Dahl S on the high-salt diet but caused largely similar relative increases in brain AT1 receptor densities in Dahl S and R on the high-salt diet versus regular salt diet. These data demonstrate that high salt intake rapidly (within 1 wk) increases AT1 receptor densities in specific brain nuclei in Dahl S and later (by 4 wk) also in Dahl R rats. Because the brain renin-angiotensin system only contributes to salt-induced hypertension in Dahl S rats, further studies are needed to determine which of the salt-induced increases in brain AT1 receptor densities contribute to the hypertension and which to other aspects of body homeostasis.

Central nervous system blockade by peripheral administration of AT1 receptor blockers.

After peripheral administration, AT(1) receptor blockers appear to be able to enter the brain and cause AT(1) receptor blockade in the central nervous system. In the current study, we investigated the effects of subcutaneous administration of embusartan versus losartan on inhibition of AT(1) receptor binding in rat brain by in vitro autoradiography. At 4 hours after single doses of 5, 30, or 100 mg/kg, both losartan and embusartan decreased iodine 125I Ang II binding dose dependently in brain structures that express AT(1) receptors both outside (e.g., organum vasculosum laminae terminalis) and within (e.g., paraventricular nucleus) the blood-brain barrier. At low doses, embusartan was twofold more potent than losartan inside but not outside the blood-brain barrier. After chronic treatment (30 mg/kg daily for 6 days), at 4 hours after the last dose, embusartan still caused more inhibition than losartan in the brain structures inside the blood-brain barrier. At 24 hours after the last dose, a modest, better inhibition for embusartan versus losartan remained: from 15% to 33% versus 10% to 24%, respectively. At 36 hours after the last dose, the inhibition for both blockers had almost completely disappeared inside the blood-brain barrier but persisted in, for example, the kidneys. These results demonstrate that-likely because of its high lipophilic character-embusartan appears to penetrate the blood-brain barrier more easily than losartan and therefore causes more effective AT(1) receptor blockade in nuclei within the blood-brain barrier.

Presence of cellular renin-angiotensin system in chromaffin cells of bovine adrenal medulla.

The presence of a local renin-angiotensin system has been established in organs that serve as angiotensin targets. In this study, the expression of angiotensinogen mRNA and subcellular localization of renin, angiotensin-converting enzyme, and angiotensin II were investigated in bovine adrenal medullary cells in primary culture. By light microscopy, expression of angiotensinogen mRNA, immunoreactive renin, angiotensin-converting enzyme, and angiotensin II were readily detectable only in the chromaffin cells. The density distribution of renin and angiotensin II in sucrose gradients suggested a concentration in chromaffin granules, a localization directly confirmed by immunoelectron microscopy. Reverse transcriptase-polymerase chain reaction and sequencing confirmed the expression of angiotensinogen in bovine chromaffin cells and the adrenal medulla. In addition, in vitro autoradiography indicated that both angiotensin-converting enzyme and angiotensin type 1 receptors were present in the adrenal medulla. These results provide the first direct evidence that chromaffin cells in the adrenal medulla are not only the target for angiotensin but should also be considered as potential local angiotensin-generating and -storing cells.