[Effect of age on the function of renin-angiotensin system]
VÁMOS Zoltán, CSÉPLÕ Péter, KOLLER Ákos
FEBRUARY 20, 2014
Hypertension and nephrology - 2014;18(01-02)
VÁMOS Zoltán, CSÉPLÕ Péter, KOLLER Ákos
FEBRUARY 20, 2014
Hypertension and nephrology - 2014;18(01-02)
[Angiotensin II (Ang II) by activating angiotensin type 1 receptors (AT1R) is one of the most potent vasoconstrictors in the regulation of vasomotor tone and thus systemic blood pressure. In this study, we hypothesized that aging alters Ang II - induced vasomotor responses and expression of vascular mRNA and protein angiotensin type 1 receptor (AT1R). Thus, carotid arteries were isolated from newborn, young, middle age, old and senescent rats and their vasomotor responses were measured in a myograph (DMT-600) to repeated administrations of Ang II. Vascular relative AT1R mRNA level was determined by qRT-PCR and the AT1R protein density was measured by Western blot. Contractions of vessels to the first administration of Ang II increased from newborn to young and middle age rats then they decreased to senescent rats. In general, second administration of Ang II elicited reduced contractions, but they also first increased and then they decreased to old age. Similarly, the AT1R mRNA level and the AT1R protein density increased from newborn to young and middle age rats then they decreased to senescent rats. The pattern of these changes correlated with functional vasomotor data. We conclude that aging (newborn to senescence) has substantial effects on Ang II-induced vasomotor responses and AT1R signaling suggesting that it is - and thus regulation of systemic blood pressure is - determined primarily by genetic programs.]
Hypertension and nephrology
[For the first time, we demonstrated the fenestration in the endothelium of the distal portion of renal afferent arteriole (AA), which is unusual among high pressure vessels. The fenestrae are co-localized with renin producing granular epithelioid cells; this arrangement makes it likely that the relatively large renin molecules may use this path to enter into the plasma. We also demonstrated that the length and area of this fenestrated segment 1) correlates with the activity of the renin-angiotensin system (RAS), 2) may change by age, in response to some stimuli such as thirst and in some diseases, 3) allows filtration of fluid prior to the glomerular filtration, which can be as high as about 30% of GFR. This morphology and the high filtration volume in AA is one of the most striking observations of renal microcirculation, and question several basic renal physiological issues.]
Hypertension and nephrology
[This review summarize the decreased physical activity and physical function of chronic kidney disease patients from the early stage of their renal disease; the favourable effects of exercise training on physical activity and function as well as on progression of chronic renal diseases. At the end, there is a recommendation for implementation of exercise in this renal patient population. The conclusion is that, on the basis of the evidences patients with chronic renal disease should be advised to increase their physical activity in all stages of their renal disea]
Hypertension and nephrology
[Hypercholesterolemia is one of the most important major risk factors that can be most influenced. Its treatment is based on guidelines. In 2013 in Hungary the common guideline of 17 societies (MKKK) as well as the recommendations of EAS/ESC and those of IAS are at disposal. These recommendations have established similar risk categories and strict LDL-cholesterol goals (<1.8 mmol/l). On 12 November, 2013, in the USA after a long drawn debate the AHA/ACC - without any lipid association - issued a new cholesterol (Ch) guideline, which drasticly differs from the existing national and European recommendations. According to AHA/ACC each patient with cardiovascular disease or diabetes should be treated with statin, irrespective of the Ch value, All patients with a LDL-Ch level over 4.9 mmol/l should also be treated with statin. In primary prevention those with values between 1.8-4.9 (LDL-Ch), or 3.5-8.0 mmol/l (Ch) would also be given statin, if their risk is more than 7.5%, with the new calculator system (“Statin Benefit Groups”). These recommendations would eliminate the classic risk categories (very-high, high, moderate risk), would abolish the system of treatment goals, as well as the regular Ch test. The non-statin therapy is not supported even in combinations. A big part of the population with low Ch level would also receive statin based on the results with the calculator, meaning that in the USA the number of those treated might double. Not only the European (e.g. EAS/,ESC) but even American societies (National Lipid Association 2013-2014) (e.g. NLA) oppose to the new guideline of AHA/ACC.]
Hypertension and nephrology
[The paper is warning for the necessity of very complex consideration before taking antihypertensive therapeutic decisions (indication, point or points of actiou, blood pressure target levels, dynamics of BP reduction, etc) for elderly hypertensive patients. Blood pressure reduction can mean efficient protection against cardiovascular events also among the elderly hypertensives. However in those old and very old hypertensive patients who have not only severe stiffness of their large vessels but suffer in advanced co-morbidities and integrated pathologic geriatric syndromes, the blood pressure reduction can result in sometimes even life threatening general deterioration. Antihypertensive therapeutic dilemmas of elderly caregivers appear mainly in relation to old hypertensive patients of age over 80 years. For this „very old” age period the HYVET study gave us evidence based conclusions about the cardiovascular protective usefulness of combined antihypertensive treatment resulting in BP reduction to 150 Hgmm systolic BP target levels. However a non-negligable rate of selection of the included patients in HYVET study can weaken the generalizability of the HYVET findings in this age period and the extensibility of its antihypertensive therapeutic conclusions for the entire „very old” population because this population has also a high proportion of patients with chronic progressive illnesses and general decline. Thus the elderly hypertensives’ caregiver must always carefully and critically balance between the messages of the HYVET and the nonselective observational follow up studies among elderlies showing frequently the so-called epidemiologic blood pressure/ mortality paradoxon. The paper is also trying to find potencial pathomechanical interpretations and point of actions for the epidemiologic blood pressure/mortality paradoxon found in the very old population.]
Hypertension and nephrology
[Introduction: Rapidly progressive glomerulonephritis is life-threatening manifestation of antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), often diagnosed only in advanced stage of renal failure. In 2010 a new histopathologic classification of ANCA- associated vasculitis was published by an international working group of nephropathologists. Vasculitis cases were classified in four groups: focal, crescent, mixed and sclerotic. Method: The aim of our study was to re-evaluate the predictive value of this new classification regarding renal outcome. From the 88 patients with ANCA-associated vasculitis treated in our department from 1996 to 2013, 39 were involved. Results: By retrospective evaluation of biopsy samples, patients were classified as 11 in focal, 12 in crescent, eight in mixed, eight in sclerotic group. There was no significant difference among the four groups regarding the mean age, sex, ANCAtype and initial eGFR. Due to the treatment, the eGFR values significantly increased in the focal and in the crescent groups. Eleven patients needed dialysis at presentation and three of them recovered, none of them belonged to the sclerotic group. The cumulative renal response to treatment was 100% in the focal, 87.5% in the mixed, 64% in the crescent and 62% in the sclerotic group. Renal response at one year treatment was 80%, thirty-one of the thirty-nine patients were dialysis independent. All patients were alive at one year, by year five two patients from the sclerotic group died. Conclusion: The new nephropathological classification of AAV is useful in predicting the renal response to treatment. Nephropathology can optimize the system by mentioning the specific percentage of normal glomeruli in the biopsy specimen.]
Hypertension and nephrology
[Affective temperaments (cyclothymic, hypertymic, depressive, anxious, irritable) are stable parts of personality and after adolescent only their minor changes are detectable. Their connections with psychopathology is well-described; depressive temperament plays role in major depression, cyclothymic temperament in bipolar II disorder, while hyperthymic temperament in bipolar I disorder. Moreover, scientific data of the last decade suggest, that affective temperaments are also associated with somatic diseases. Cyclothymic temperament is supposed to have the closest connection with hypertension. The prevalence of hypertension is higher parallel with the presence of dominant cyclothymic affective temperament and in this condition the frequency of cardiovascular complications in hypertensive patients was also described to be higher. In chronic hypertensive patients cyclothymic temperament score is positively associated with systolic blood pressure and in women with the earlier development of hypertension. The background of these associations is probably based on the more prevalent presence of common risk factors (smoking, obesity, alcoholism) with more pronounced cyclothymic temperament. The scientific importance of the research of the associations of personality traits including affective temperaments with somatic disorders can help in the identification of higher risk patient subgroups.]
Lege Artis Medicinae
[Diuretics have remained the cornerstone of the antihypertensive treatment since their widespreading in the 1960s. According to the 2018 ESC/ESH Guidelines for the management of arterial hypertension, in the absence of evidence from direct comparator trials and recognizing that many of the approved single-pill combinations are based on hydrochlorothiazide, this drug and thiazide-like indapamide can be considered suitable antihypertensive agents. In the 2018 Hungarian guidelines indapamide is named as the most efficacious diuretic in the treatment of patients with hypertension. The aim of the publication is redefining thiazide- and thiazide-like diuretic use in the treatment of hypertensive patients, with particular attention to presently available hydrochlorothiazide and indapamide, and their combination drugs in Hungary.]
Lege Artis Medicinae
[Chronic obstructive pulmonary disease is a very common comorbidity of hypertension and it is often unrecognised by physicians. The factors involved in the pathomechanism of both diseases should be realised when choosing treatment. Among factors, hypoxia, increased tone of sympathetic nervous system and activation of renin-angiotensin-aldosterone system should primarily be considered. Vascular wall damage and endothelial dysfunction has an important role in both conditions. The goals of treatment are elimination of risk factors, optimizing the blood pressure, the consequential prevention of cardio-cerebrovascular, renal and pulmonary damage; finally prolonging the patients’ life and improving their quality of life as well. Both hypertension and COPD significantly worsen the condition of COVID-19 patients since they increase the severity of the disease and the rate of in-patients’ and their mortality. In the treatment of hypertension among COPD and COVID-19 patients there must be emphasized the medication inhibiting of renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme inhibitors or angiotensin-II AT1 receptor antagonists. Special attention concerned the beneficial effect of mineralocorticoid receptor antagonist spironolactone. Other antihypertensive drugs (calcium channel blockers, thiazide-like diuretics, high selectivity β1 receptor antagonists) may supplement the treatment if necessary. Long-acting β2 receptor agonists, muscarinic receptor antagonists and inhalation corticosteroids may be administered in double or triple combination also in hypertension and COPD as well. It is important to note, that statin therapy and also vitamin D3 improve the condition of COVID-19 patients.]
Hypertension and nephrology
[Purpose: Monitoring the effectiveness and safety of the fix combination formulation Egiramlon® therapy containing ramipril and amlodipin in patients, suffering from mild or moderate hypertension despite antihypertensive treatment. Patients and methods: Open, prospective, phase IV clinical observational study, which involved 9169 patients (age >18) with mild or moderate hypertension [TUKEB No: 16927- 1/2012/EKU (294/PI/12.)]. Ramipril/Amlodipin 5/5, 5/10, 10/5, 10/10 mg combinations were administered/ titrated in three visits, during the four months period according to the physician’s decision Blood pressure was measured by validated blood pressure sphygmomanometry and ABPM (Meditech, Hungary). The dosis of the fix combination formulation was determined individually during the visits by the 923 doctors involved in the study. The target blood pressure value was 140/90 mmHg, but in case of high risk patients population (diagnosed cardiovascular disease, diabetes), 130/90 mmHg target value was determined. Results: In 70.1% of the patients had no protocoll deviation. Patients data and examination results were processed according to this 6423 patient population. The average age of the patients were 60.2 year, in 50-50% sex distribution. The average duration of the treated hypertension was 9.8 years and the average blood pressure value was 157/91 mmHg. Till the end of the study, systolic blood pressure has decreased with 26.4 mmHg and diastolic pressure with 11.8 mmHg. An average 5.5 bpm heart rate frequency decreasing was observed at the end of the study. As a result of the treatment 52.4% of the patient population has reached the target blood pressure value.]
Lege Artis Medicinae
[Hypertension prevalence and cardiovascular risk gradually with age. However this aging process seems to take a more rapid course in some individuals, as reflected in the Early Vascular Aging (EVA) syndrome. Age and high blood pressure are the two main determinants of arterial stiffness which is the core of EVA: the impaired elasticity of the media layer of large elastic arteries (mainly the aorta), a process that can be measured by pulse wave velocity. In elderly hypertensives, large arteries stiffen and systolic and pulse pressures increase, due to wave reflections. Arterial stiffness has predictive value for future CV e.g. events, coronary artery disease, stroke, and vascular dementia and even all-cause mortality. The concepts of EVA (Early Vascular Aging) and SUPERNOVA (Supernormal Vascular Aging, the opposite phenotype of EVA) help to understand why early target-organ damages develop in some individuals and why others remain much more “younger” than their chronologic age. New drugs are being developed to treat EVA when lifestyle intervention and conventional risk factor controlling drugs are not enough.]
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