Green tea could improve elderly hypertension by modulating arterial stiffness, the activity of the renin/angiotensin/aldosterone axis, and the sodium-potassium pumps in old male rats.

Hypertension is a major health problem common in the elderly people. Green tea is a popular beverage recommended in folk medicine for lowering blood pressure. However, the molecular mechanisms involved in the antihypertensive effects of green tea are not fully understood. Therefore, the aim of this study was to investigate the antihypertensive effects of green tea on high-salt diet-induced hypertension in old male rats. Forty old male rats were divided into five groups: control, hypertensive, and hypertensive-green tea (2, 4, and 6 g/kg). Heart rate (HR) and systolic blood pressure (SBP) were measured. Cardiac and renal histology were also performed. Lipid profile, NO, angiotensin II (Ang II), and aldosterone were determined, and the expression of eNOS, ATIR and ATIIR, aldosterone receptor, and Atp1a1 were measured. Green tea could significantly decrease HR and SBP, lipid profiles, renin-angiotensin II-aldosterone system activity, and Ang II signaling in kidney tissue of hypertensive rats (p < .01). It also increased Atp1a1, Nrf2, and eNOS expression along with antioxidant enzymes activity and NO concentration (p < .05) and decreased NF-ĸB and iNOS expression and IL-1ß levels in the heart, kidneys, and aorta of rats with hypertension. It can be concluded that green tea can improve salt-induced blood pressure by modulating the function of the renin-angiotensin-aldosterone system, enhancing the synthesis of nitric oxide in the endothelium, increasing antioxidant activity and suppressing inflammation in the heart and kidney, improving the expression of the sodium-potassium pump, and reduction in serum lipids and glucose in aged male rats. PRACTICAL APPLICATIONS: The results of this study showed that green tea could improve hypertension in elderly rats by modulating (1) the expression of the sodium-potassium pump in the heart, kidney, and aortic tissues, (2) the activity of the renin-angiotensin II-aldosterone system in kidney, (3) enhancing antioxidant and anti-inflammatory activities in the heart, aorta, and kidneys, (4) enhancing the synthesis of nitric oxide in the endothelium, and (5) lowering lipid profile. The results of these studies show that the consumption of green tea and its products can be a good candidate for the prevention of cardiovascular diseases such as hypertension in the elderly. In addition, attention to its bioactive compounds can be considered by researchers as an independent therapeutic strategy or adjunctive therapy for the treatment of hypertension.

Plasma renin, aldosterone, and urinary prostaglandin E2 levels in children with hypocalcemia due to vitamin D deficiency rickets.

We investigated the effect of hypocalcemia on plasma renin, aldosterone, and urine PGE2 levels in children with vitamin D deficiency rickets (VDDR). In the study group, 25 patients with VDDR-induced hypocalcemia were treated with a single dose of 150,000-300,000 IU cholecalciferol and 50 mg/kg/day elemental Ca for 10 days. On any day between 21th and 30th days after the treatment, the patients' clinical, biochemical and radiologic findings were re-evaluated. The healthy children with the same sex and similar age as the study group comprised the control group. Plasma sodium (Na), potassium (K), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), 25- hydroxy vitamin D (25OHD), renin, aldosterone; and urinary Ca, creatinine (Cr) and prostaglandin E2 (PGE2) levels were measured in both the study (pre-treatment and post-treatment) and the control group. Plasma Ca, P, 25OHD and renin levels and urinary PGE2/Cr ratio in the post-treatment group were significantly higher than those in the pre-treatment group while K, ALP, and PTH concentrations were significantly lower. Plasma ALP and PTH levels in pre-treatment group were significantly higher than in the control group while Ca, P, 25OHD, aldosterone and renin concentrations and urinary PGE2/Cr ratio were significantly lower. Post-treatment plasma Ca level was significantly decreased in normal limits compared to the control group while other biochemical parameters were not different from the control group. Plasma Ca concentration was positively correlated with renin level and urinary PGE2/Cr ratio. The findings suggest that hypocalcemia may inhibit the production of renin, aldosterone and PGE2 and a blunt aldosterone secretion may develop even after recovery from hypocalcemia.

Aldosterone Decreases Vasopressin-Stimulated Water Reabsorption in Rat Inner Medullary Collecting Ducts.

Aldosterone indirectly regulates water reabsorption in the distal tubule by regulating sodium reabsorption. However, the direct effect of aldosterone on vasopressin-regulated water and urea permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether aldosterone regulates osmotic water permeability in isolated perfused rat IMCDs. Adding aldosterone (500 nM) to the bath significantly decreased osmotic water permeability in the presence of vasopressin (50 pM) in both male and female rat IMCDs. Aldosterone significantly decreased aquaporin-2 (AQP2) phosphorylation at S256 but did not change it at S261. Previous studies show that aldosterone can act both genomically and non-genomically. We tested the mechanism by which aldosterone attenuates osmotic water permeability. Blockade of gene transcription with actinomycin D did not reverse aldosterone-attenuated osmotic water permeability. In addition to AQP2, the urea transporter UT-A1 contributes to vasopressin-regulated urine concentrating ability. We tested aldosterone-regulated urea permeability in vasopressin-treated IMCDs. Blockade of gene transcription did not reverse aldosterone-attenuated urea permeability. In conclusion, aldosterone directly regulates water reabsorption through a non-genomic mechanism. Aldosterone-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. There may be a sex difference apparent in the inhibitory effect of aldosterone on water reabsorption in the inner medullary collecting duct. This study is the first to show a direct effect of aldosterone to inhibit vasopressin-stimulated osmotic water permeability and urea permeability in perfused rat IMCDs.

[Supportive care for malignant ascites in palliative phase: Place of paracentesis and diuretics]. / Prise en charge symptomatique de l'ascite maligne en phase palliative: place de la paracentèse et des diurétiques.

Malignant ascites, occurring in advanced stages of cancer, is linked with poor prognosis and can cause invalidating symptoms. Physiopathological mechanisms of ascites formation are complex and have yet to be fully elucidated. In most cases, ascites is due to peritoneal carcinomatosis in which vascular permeability is enhanced by VEGF production while lymphatic drainage decreases. Ascites can also be secondary to portal hypertension, for example in case of multiple liver metastases, or due to lymphatic obstruction. While paracentesis and diuretics are commonly used, their efficiency has never been compared in a randomized controlled study. Paracentesis brings immediate but temporary relief in over 90% of cases, and implies multiple hospitalizations. Literature reports ascites control by aldosterone alone or in association with furosemide. But, available data is controversial, and there is no predictive factor to identify patients that respond to diuretic treatment. The indication of diuretic treatment is left to the appreciation of physicians. Existing recommendations are old, and practices influenced by results obtained in non-neoplastic ascites. Additional evidences are required before guidelines can be established for the palliative management of malignant ascites.

Low dose combination steroids control autoimmune mouse hearing loss.

The severe side effects of glucocorticoids prevent long term management of hearing loss. Alternative steroid treatments that minimize or eliminate these effects would significantly benefit therapeutic control of hearing disorders. A steroid treatment study of autoimmune mouse hearing loss was conducted to determine the efficacy of combining aldosterone and prednisolone at low doses. An assessment also was made of low dose fludrocortisone, a synthetic mineralocorticoid that also has a slight glucocorticoid effect. MRL/MpJ-Fas(lpr) mice were tested for baseline ABR thresholds at 3 months of age and then treated with aldosterone (3.0 µg/kg) or prednisolone (1.0 mg/kg) to determine the lowest effective dose of each. Other mice were given the two steroids in combination at doses of Pred 0.5 mg+Aldo 1.5 µg; Pred 1.0 mg+Aldo 3.0 µg; or Pred 1.5 mg+Aldo 5.0 µg. Mice were retested with ABR at 1 and 2 months to determine the efficacy of the different steroid treatments in controlling hearing loss. Another series of mice were given the synthetic mineralocorticoid fludrocortisone at low (2.8 µg/kg) or high (10 µg/kg) doses and retested at monthly intervals for 3 months. Autoimmune mouse hearing loss developed in untreated controls. This threshold elevation was not prevented by prednisolone at 1 mg/kg or by aldosterone at 3 µg/kg when each was given alone. However, the two steroids combined at these doses effectively controlled hearing loss. The fludrocortisone treatments also were effective at low doses in preventing or reversing the autoimmune mouse hearing loss. This efficacy of combined steroids at low doses suggests the potential for reducing the side effects of glucocorticoids in the therapeutic control of hearing disorders.

Manejo del hiperaldosteronismo primario en la provincia de Cáceres. Experiencia de 20 años / Management of primary hiperaldosteronism in the Cáceres province. Twenty-year experience

El hiperaldosteronismo primario (HA1.º) es una forma secundaria de hipertensión arterial (HTA) de fácil diagnóstico, provocado por la secreción inadecuada de aldosterona por la corteza suprarrenal. Con el objeto de establecer las principales características clínicas y bioquímicas de estos pacientes revisamos la base de datos de los últimos 20 años de la consulta monográfica de HTA del Servicio de Nefrología del Hospital San Pedro de Alcántara. De los 937 pacientes con HTA de origen no renal, 16 fueron diagnosticados de HA1.º (1,7 por ciento). No encontramos diferencias en cuanto al sexo. La media de edad fue de 45,8 +/- 9,28 años. Sólo 10 de los 16 presentaban clínica sugerente de HA1.º La tensión arterial (TA) media en la primera consulta fue de 161 +/- 19/101 +/- 13 mmHg. La repercusión orgánica en el momento del diagnóstico era grado II en el 50 por ciento de los casos y grado I en el 50 por ciento restante. Se constató hipopotasemia en 10 pacientes; los 6 restantes presentaban niveles de potasio normales. En todos encontramos niveles elevados de aldosterona basal; en 2 casos la renina no se encontraba suprimida. La gammagrafía con yodo-colesterol permitió localizar la lesión en 13 de los 16 pacientes; la tomografía axial computarizada y la resonancia magnética identificaron 2 casos confirmados por el test postural y la respuesta quirúrgica; en un caso no pudo establecerse la localización. Se diagnosticaron 8 adenomas y 7 hiperplasias bilaterales. Se intervinieron quirúrgicamente 5 de los adenomas, permaneciendo 3 pacientes normotensos son tratamiento y dos con buena respuesta ( cifras de TA normales con dosis bajas de espironolactona). Las hiperplasias, los adenomas no intervenidos y el caso no localizado presentan cifras de TA normales con dosis bajas de espironolactona (AU)

Pseudohypoaldosteronism in eight families: different forms of inheritance are evidence for various genetic defects.

Pseudohypoaldosteronism is a rare hereditary disorder presenting in early infancy with renal salt loss leading to hyponatremia and hyperkalemia despite high levels of plasma aldosterone. The patients are insensitive to mineralocorticoids; however, sodium supplementation is able to correct electrolyte abnormalities. Absent or greatly diminished type I aldosterone receptors in peripheral mononuclear leucocytes have been recently demonstrated and explain the lack of response to mineralocorticoids. We have studied the mode of inheritance in eight families with a total of nine patients. There was evidence for an autosomal recessive form of inheritance in four families, while the other four families appeared to have an autosomal dominant mode of transmission. In three families the autosomal recessive form was characterized by normal receptor as well as hormone data in both parents, while in one family receptor levels in both parents were greatly reduced, but hormone levels were normal. In the four families with an autosomal dominant mode of transmission there was always one parent with reduced receptor binding in peripheral mononuclear leucocytes and elevated serum hormone levels. These parents were entirely asymptomatic. In an extended family we were able to study an aunt and her newborn daughter, who were both also biochemically affected but clinically asymptomatic. It, therefore, appears that this dual pattern of genetic transmission may indicate differing genetic defects which cause the same clinical picture of pseudohypoaldosteronism.

[Prevention of brain edema. After acute hypertonic dehydration by dexamethasone, aldosterone and spirolactone during rehydration]. / Prophylaxe des Hirnödems mit Dexamethason, Aldosteron und Spironolacton im Tiermodell nach akuter, hypertoner Dehydratation.

The brain edema preventing effects of aldosterone and spirolactone were compared to the effects of dexamethasone in young rabbits, dehydrated by enteral application of Na2SO4-solution. The water-, sodium- and potassium content of total brains were measured after a four hour period of forced glucose infusion. The water content of the treated groups did not differ from the control group, whereas the electrolyte content differed significantly. Dexamethasone lowered the sodium content below normal value. Spirolactone treatment resulted in an elevated potassium content. It is assumed, that aldosterone and spirolactone in pharmacological doses act, like dexamethasone, by nonspecific effects on the blood-brain-barrier and cell membranes. The generally accepted principle of slow rehydration after hypertonic dehydration may have an additional beneficial effect by sustaining secondary hyperaldosteronism.

Orally active mineralocorticoid agonists and antagonists: delta 1-derivatives of aldosterone and 18-deoxyaldosterone.

The effect of delta 1 unsaturation on the oral effectiveness of a representative mineralocorticoid agonist and antagonist was investigated in an adrenalectomized rat bioassay. Dehydrogenation at the 1.2 position did not alter the qualitative nature of the mineralocorticoid activity of the parent compound. Thus delta 1-aldosterone (21,18-dihydroxy-11 beta, 18-oxido-1,4-pregnadiene-3,20-dione) retained pure mineralocorticoid agonism, and delta 1-18-deoxyaldosterone (21-hydroxy-11 beta, 18-oxido-1,4-pregnadiene-3,20-dione)demonstrated the same relative degree of predominant antagonism as 18-deoxyaldosterone (21-hydroxy-11 beta, 18-oxido-4-=pregnene-3,20-dione) itself. In each instance, receptor affinity was diminished by 1,2 unsaturation, but this effect was offset by the greater bioavailability of the delta 1 derivatives on oral administration. (Endocrinology 108: 517, 1981)

Haemodynamic effects of different corticosteroids in controlled haemorrhagic shock in the dog.

The haemodynamic effects of massive doses of hydrocortisone (80-320 mg.kg-1), methylprednisolone (4-32 mg.kg-1), betamethasone (1.6-12.8 mg.kg-1) and aldosterone (0.1-0.8 mg.kg-1) and the interaction with phenoxybenzamine and propranolol have been studied during controlled haemorrhagic shock in the anaesthetized dog. Hydrocortisone was the only steroid which showed any significant vasodilating ability when given alone. The alpha-receptor blocking agent phenoxybenzamine distinctly decreased the total peripheral resistance. The effect of the phenoxybenzamine was increased in combination with hydrocortisone or methylprednisolone, especially if the steroid was given as the first drug. The vasodilation found was efficiently abolished by the beta-receptor blocking agent propranolol. The ability of hydrocortisone or methylprednisolone to potentiate phenoxybenzamine was not shared by betamethasone or aldosterone. Thus, the haemodynamic effect of the steroid does not seem to be correlated to either a glucocorticoid nor a mineralocorticoid effect. It is suggested that the steroid effect studied is related to the ability of hydrocortisone or methylprednisolone to block the extra neuronal amine uptake which decreases the rate of elimination of the sympathetic transmitter from the vicinity of the adrenergic receptor of the vascular smooth muscle.