RESUMO
The effects of a novel calcium transport antagonist, nisoldipine, on K-stimulated aldosterone secretion have been examined in vivo. Direct KCl infusion into the adrenal gland stimulated aldosterone secretion. Infusion of nisoldipine, concomitantly with KCl at two rates, abolished the stimulation of aldosterone independently of its effects on K transport. The results suggest that K stimulation of aldosterone secretion in vivo is at least in part mediated by alterations in transmembrane Ca flux.
Assuntos
Glândulas Suprarrenais/metabolismo , Aldosterona/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Nifedipino/análogos & derivados , Cloreto de Potássio/farmacologia , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Feminino , Hidrocortisona/metabolismo , Cinética , Nifedipino/farmacologia , Nisoldipino , OvinosRESUMO
The homeostasis of cytosolic free calcium ([Ca2+]i) and intracellular free sodium ([Na+]i) are linked in many cell types. We, therefore, studied the effect on [Na+]i of two physiological stimulators of aldosterone synthesis that trigger the calcium messenger system, angiotensin-II (Ang II) and potassium ion (K+), in cultured bovine adrenal glomerulosa cells, using the intracellular fluorescent probe for sodium, sodium benzofuran isophthalate. Ang II induced a concentration-dependent and sustained increase in [Na+]i, from a resting value of 9.2 +/- 3.5 to a maximum of 48.5 +/- 5.5 mM (n = 14). This [Na+]i response was mediated by receptors of the AT1 subtype, because it was abolished by losartan (DuP 753). K+ (15 mM) induced a weaker [Na+]i response, from 5.9 +/- 2.6 to 16.8 +/- 2.5 mM (n = 9). In freshly prepared cells, basal [Na+]i was significantly higher (23.9 +/- 1.8 mM; n = 14; P < 0.01) than in cultured cells. Atrial natriuretic peptide, which is known to affect sodium transport in various cell types, did not alter the [Na+]i response elicited by Ang II. Ethylisopropylamiloride, an inhibitor of Na+/H+ exchange, and dichlorobenzamyl, an inhibitor of Na+/Ca2+ exchange, both inhibited in a concentration-dependent manner the Ang II- and K(+)-induced aldosterone response. Isoosmotic replacement of extracellular Na+ markedly reduced basal aldosterone synthesis. Under these conditions, the concentration-response curve for Ang II-induced aldosterone synthesis was shifted to the right, and its maximum was strikingly diminished. These results show that Ang II and, to a lesser extent, K+ induce significant changes in [Na+]i in bovine glomerulosa cells. These [Na+]i changes probably occur through the Na+/H+ and Na+/Ca2+ exchangers and are likely to play a role in activation of the steroidogenic cascade.
Assuntos
Aldosterona/biossíntese , Angiotensina II/farmacologia , Sódio/metabolismo , Zona Glomerulosa/metabolismo , Animais , Fator Natriurético Atrial/farmacologia , Benzofuranos , Transporte Biológico , Proteínas de Transporte/metabolismo , Bovinos , Células Cultivadas , Citosol/metabolismo , Éteres Cíclicos , Corantes Fluorescentes , Homeostase , Potássio/farmacologia , Trocador de Sódio e Cálcio , Zona Glomerulosa/efeitos dos fármacosRESUMO
The characteristics of the change in cytosolic free Ca2+ concentration ([Ca2+]i) in response to agonist stimulation were studied in individual cells of the bovine adrenal zona glomerulosa. Following digestion and dispersion, the cells were loaded with the fluorescent Ca2+ indicator fura-2. The cells adhered to Concanavalin A-coated coverslips and were studied using dual excitation wavelength microfluorimetry. In this procedure individual cells under constant perfusion are visualized by microscopy and excited with light alternating rapidly between 340 and 380 nm. The ratio of fluorescence (F) emitted from the cell (F340/F380) correlates directly with [Ca2+]i. Continuous stimulation with angiotensin II (AII; 10 nmol/l) resulted in a brisk transient rise in [Ca2+]i within 8 s of application of the stimulus. In 50% of cells studied, this initial peak was followed by a series of oscillations in [Ca2+]i lasting up to 13 min, with an average period of 33.0 +/- 5.9 (S.E.M.) seconds. [Ca2+]i did not return to prestimulation levels and, subsequent to the oscillatory phase, the [Ca2+]i remained increased for several minutes. Upon removal of extracellular Ca2+ the oscillations ceased almost immediately although [Ca2+]i remained increased. However, in Ca2+-free medium, a single peak of [Ca2+]i still occurred in response to AII. Cells remained refractory to restimulation over a 15-min period. In contrast, stimulation with K+ (8 mmol/l) rapidly increased [Ca2+]i to a level similar to that induced by AII but without inducing oscillations. Moreover, the effect lasted only while K+ was present and was highly reproducible over multiple stimulations during a 15-min period. These results corroborate, at the single cell level, the known action of AII of causing release of intracellular Ca2+, but reveal a more complex mechanism of action on Ca2+ influx than previously recognized, possibly invoking a role for a putative second messenger-operated membrane Ca2+ channel.
Assuntos
Angiotensina II/farmacologia , Cálcio/metabolismo , Citosol/metabolismo , Zona Glomerulosa/metabolismo , Angiotensina II/administração & dosagem , Animais , Bovinos , Separação Celular , Potássio/farmacologia , Zona Glomerulosa/efeitos dos fármacosRESUMO
Although both angiotensin II (Ang II) and potassium ion (K+) induce marked elevations of cytosolic free calcium concentration, [Ca2+]c, in adrenal zona glomerulosa cells-an effect which is thought to trigger aldosterone synthesis-Ang II is also known to reduce the sustained [Ca2+]c rise induced by K+. We have examined whether this effect of Ang II on the calcium messenger system is reflected at the level of the final biological response, aldosterone synthesis. In superfused isolated rat glomerulosa cells, K+ (8 mM) induced a sustained, 60-fold increase in aldosterone production. In contrast, the maximal response to Ang II (10 nM) amounted to only 10 times the basal production. When added subsequent to K+ stimulation, Ang II provoked an immediate and dramatic drop in aldosterone synthesis, to levels obtained with Ang II alone. Under conditions of maximal K+ stimulation, this effect depended upon Ang II concentration, while the well-known synergistic effect was observed with submaximal concentrations of both agonists. The inhibitory effect of Ang II could be reproduced with dioctanoylglycerol, a selective activator of protein kinase C. By contrast, the aldosterone response to adrenocorticotropic hormone (ACTH) was not affected by Ang II. At submaximal concentrations of ACTH, the steroidogenic effect of Ang II was even additive to that of ACTH. Thus, we have shown that, under conditions of maximal stimulation, Ang II exerts a profound inhibition of steroidogenesis in K(+)-stimulated rat adrenal glomerulosa cells. This counter-regulatory mechanism may ensure adequate levels of aldosterone production in vivo.
Assuntos
Aldosterona/biossíntese , Angiotensina II/farmacologia , Zona Glomerulosa/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Masculino , Potássio/farmacologia , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Zona Glomerulosa/citologia , Zona Glomerulosa/efeitos dos fármacosRESUMO
Molecular cytogenetic and developmental assessment was performed on 50 individuals with cri-du-chat syndrome. Fluorescent in situ hybridization analysis was used to confirm a terminal deletion karyotype and map more precisely the location of the deletion breakpoint. We identified terminal deletion breakpoints mapping from 5p15.2 to 5p13. Developmental assessment was performed using the Vineland Adaptive Behavior Scales test. Composite Vineland Scores ranged from 20-75. In general, the communication score was higher than the composite score. Comparison of the size of the deletion with the composite Vineland score, as well as the Vineland Communication score, demonstrated that there was no correlation between the size of the deletion and the level of developmental delay. These results demonstrate that patients with cri-du-chat syndrome show high variability in the level of developmental achievement.
Assuntos
Deleção Cromossômica , Síndrome de Cri-du-Chat/genética , Síndrome de Cri-du-Chat/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Cromossomos Humanos Par 5/genética , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Mapeamento Físico do Cromossomo , Estatística como Assunto , Fatores de TempoRESUMO
PURPOSE: This study was undertaken in order to investigate whether the production of vasodilatory prostaglandins is increased in the retinal vasculature of the diabetic rat. METHODS: Diabetes was induced in male Sprague-Dawley rats using streptozotocin. Diabetic rats were left uncontrolled for 3-4 weeks or were treated with insulin replacement throughout the period of diabetes. Control rats were age-matched. Retinal vessels extracted from retinae removed at sacrifice were incubated in a physiological salts solution. Prostaglandin E and prostaglandin I2 were measured in collected medium. RESULTS: The production of both prostaglandin E and prostaglandin I2 by blood vessels isolated from the retina was increased by approximately 40% in streptozotocin-diabetic rats, compared to controls, within 4 weeks of the onset of diabetes. This increase was reversed by treatment of streptozotocin-diabetic rats with insulin. The increase in prostaglandin production was not due to alteration in the maximal capacity of cyclooxygenase enzyme. CONCLUSIONS: Increased production of vasodilatory prostaglandins occurs in the rat retinal vasculature early in diabetes. Prostaglandins may contribute to altered retinal hemodynamics in early diabetic retinopathy.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Epoprostenol/biossíntese , Prostaglandinas E/biossíntese , Vasos Retinianos/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Insulina/uso terapêutico , Masculino , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Vasos Retinianos/efeitos dos fármacosRESUMO
Sheep whose left adrenal gland had been autotransplanted to a combined carotid artery-jugular vein skin loop in the neck were used to study the role of calcium in stimulus-secretion coupling for aldosterone biosynthesis. The calcium antagonists nisoldipine and verapamil were infused directly into the adrenal arterial blood supply during Na depletion or in Na replete sheep during concomitant adrenal arterial infusion of angiotensin II or KC1. The stimulation of aldosterone secretion following angiotensin II (1 nmol/l blood flow) or KC1 (delta [K] 1 mmol/l blood flow) was totally blocked by both verapamil (10(-4) mol/l blood flow) and nisoldipine (2.6 X 10(-6) mol/l blood flow). In contrast, neither antagonist had any significant effect on the established hypersecretion of aldosterone caused by 24 h Na depletion as a result of parotid salivary loss. The data suggest an important role for calcium in stimulus-secretion coupling during acute stimulation by K and angiotensin II, but not in the longer-term sodium depletion. The data further suggest that angiotensin may not be the sole sustaining stimulus to aldosterone in sodium depletion or its mechanism switches from a Ca-dependent to a Ca-independent mechanism with Na depletion.
Assuntos
Aldosterona/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Glândulas Suprarrenais/transplante , Angiotensina II/fisiologia , Animais , Cálcio/fisiologia , Nifedipino/análogos & derivados , Nifedipino/farmacologia , Nisoldipino , Potássio/fisiologia , Ovinos , Sódio/deficiência , Transplante Autólogo , Verapamil/farmacologiaAssuntos
Deficiência do Fator XI/genética , Doenças de von Willebrand/genética , Adolescente , Adulto , Tempo de Sangramento , Transfusão de Sangue , Criança , Fator VIII/análise , Deficiência do Fator XI/imunologia , Deficiência do Fator XI/terapia , Feminino , Antígenos HLA/análise , Humanos , Imunoeletroforese Bidimensional , Tempo de Tromboplastina Parcial , Adesividade Plaquetária , Doenças de von Willebrand/imunologia , Doenças de von Willebrand/terapiaRESUMO
BACKGROUND: Computerized ambulatory monitoring provides real-time assessments of clinical outcomes in natural contexts, and it has been increasingly applied in recent years to investigate symptom expression in a wide range of disorders. The purpose of this study was to examine the feasibility and validity of this data collection strategy with adult stroke patients. METHODS: Forty-eight individuals (75% of the contacted sample) agreed to participate in the current study and were instructed to complete electronic interviews using a personal digital assistant 5 times per day over a 1-week period. RESULTS: More than 80% of programmed assessments were completed by the sample, and no evidence was found for fatigue effects. Expected patterns of associations were observed among daily life variables, and data collected through ambulatory monitoring were significantly correlated with standard clinic-based measures of similar constructs. CONCLUSION: Support was found for the feasibility and validity of computerized ambulatory monitoring with stroke patients. The application of these novel methods with stroke patients should provide complementary information that is inaccessible to standard hospital-based assessments and permit increased understanding of the significance of clinical results and test scores for daily life experience.
Assuntos
Monitorização Ambulatorial/métodos , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Afeto/fisiologia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/normas , Testes Neuropsicológicos/normas , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Diabetic retinopathy remains a major cause of loss of vision. The Diabetes Control and Complications Trial (DCCT) has implicated hyperglycaemia as a probable major direct causative factor in the pathogenesis of diabetic retinopathy. There are several plausible mechanisms by which high glucose concentrations could lead to the functional and later structural changes characterising diabetic retinopathy. These include increased activity of the aldose reductase pathway, increase de novo synthesis of diacylglycerol from glucose, causing protein kinase C activation, increased non-enzymatic glycation and increased oxidative damage. The demonstration of the potential roles of these pathways and the subsequent effects of growth factors in enhancing angiogenesis provide potential new approaches to the prevention and treatment of diabetic retinopathy.
Assuntos
Retinopatia Diabética/etiologia , Hiperglicemia/complicações , Aldeído Redutase/fisiologia , Animais , Glicemia/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/terapia , Produtos Finais de Glicação Avançada/fisiologia , Humanos , Hiperglicemia/sangue , Retina/patologia , Retina/fisiopatologiaRESUMO
We report on a father and son who have an interstitial deletion of 5p14. The father is clinically and mentally normal while the son has significant clinical involvement including microcephaly, seizures, and global developmental delay. The extent of the 5p14 deletion was determined using fluorescence in situ hybridisation (FISH). The deletion in this present family is smaller than a deletion previously described in a multigenerational family that lacks any clinical phenotype. This report shows that a 5p14 deletion does not always lead to a normal phenotype.
Assuntos
Cromossomos Humanos Par 5 , Deleção de Genes , Microcefalia/genética , Convulsões/genética , Pré-Escolar , Cromossomos Artificiais de Levedura , Fácies , Humanos , Hibridização in Situ Fluorescente , Masculino , Modelos Genéticos , FenótipoRESUMO
Linkage studies have suggested a locus for bipolar disorder as well as schizophrenia in the pericentric region of chromosome 18. Several candidate genes have been identified in the region including ACTH, IMP, and G(olf), however no reports of mutations in families showing linkage to the 18p11 locus have been reported. Recently, mild linkage disequilibrium has been observed with a polymorphic marker that maps within the G(olf) gene and schizophrenia in families from Germany and Israel, suggesting that a gene mapping near G(olf) may be involved in psychiatric disorders. A BAC and cosmid contig around the G(olf) locus has been generated and BAC clones were used for cDNA selection experiments. Several novel genes have been identified which are expressed in the brain. These genes may be possible candidate genes for psychiatric illness.
Assuntos
Transtorno Bipolar/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 18 , Esquizofrenia/genética , Cosmídeos , Primers do DNA , DNA Complementar , Saúde da Família , Ligação Genética , Humanos , Reação em Cadeia da PolimeraseRESUMO
Most patients with cri-du-chat syndrome have a de novo deletion of the short arm of chromosome 5 (5p). In order to perform extensive phenotype-genotype correlation studies, a relatively easy method for the precise determination of the extent of a patient's deletion is essential. Towards this purpose, a set of minimally overlapping YAC clones that span 5p was identified. A BAC that maps at or near the 5p telomere was also used. A total of 110 patients with previously determined de novo terminal deletions by standard cytogenetic approaches were reanalyzed using the YAC clones and fluorescent in situ hybridization (FISH). Of the 110 samples, 4 patients were determined to have interstitial deletions, 1 patient had an unbalanced translocation, and no deletion could be detected in 2 patients. The FISH results in the 7 patients affect the clinical prognosis for some of these patients. These results demonstrate the need for supplementing standard cytogenetics with FISH analysis when an abnormal karyotype is detected.
Assuntos
Deleção Cromossômica , Síndrome de Cri-du-Chat/diagnóstico , Síndrome de Cri-du-Chat/genética , Hibridização in Situ Fluorescente/métodos , Criança , Pré-Escolar , Cromossomos Humanos Par 5/genética , Mapeamento de Sequências Contíguas , Síndrome de Cri-du-Chat/sangue , Sondas de DNA , Diagnóstico Diferencial , Humanos , Lactente , Recém-Nascido , TelômeroRESUMO
In this short review, the cellular mode of action of angiotensin II and arginine-vasopressin is described with emphasis on the transmembrane signalling system. Two target cells are considered: the zona glomerulosa cell of the adrenal gland and the vascular smooth muscle cell. The information provided should help practitioners in endocrinology and hypertension to understand the physiological concepts which are expected to form the basis for future therapeutic developments.
Assuntos
Angiotensina II/fisiologia , Vasopressinas/fisiologia , Animais , Cálcio/metabolismo , Diglicerídeos/fisiologia , Mesângio Glomerular/fisiologia , Humanos , Hidrogênio/fisiologia , Inositol 1,4,5-Trifosfato/fisiologia , Músculo Liso Vascular/fisiologia , Proteína Quinase C/fisiologia , Receptores de Angiotensina/fisiologia , Transdução de Sinais/fisiologia , Sódio/fisiologia , Zona Glomerulosa/fisiologiaRESUMO
This study determined the proficiencies of laboratories measuring human immunodeficiency virus type 1 (HIV-1) viral loads and the accuracies of two assays used for HIV-1 viral load measurement in Australia and investigated the variability of the new versions of these assays. Quality assessment program panels containing (i) dilutions of HIV-1 subtype B, (ii) replicates of identical samples of HIV-1 subtype B, and (iii) samples of subtype E and B were tested by laboratories. Total variability (within and between laboratories) was tested with quality control samples. The coefficients of variation (CVs) for the Roche AMPLICOR HIV-1 MONITOR version (v) 1.0 and Chiron Quantiplex bDNA 2.0 assays ranged from 53 to 87% and 22 to 31%, respectively. The widespread occurrence of invalid runs with the AMPLICOR HIV-1 MONITOR 1.0 assay was identified. The CVs of the new versions of the assays were 82 to 86% for the AMPLICOR HIV-1 MONITOR v 1.5 assay and 16 to 23% for the Quantiplex bDNA 3.0 assay. For virus dilution samples, all but 5 of 19 laboratories obtained results within 2 standard deviations of the mean. The Quantiplex bDNA 2.0 assay reported values lower than those reported by the AMPLICOR HIV-1 MONITOR version 1.0 assay for samples containing HIV-1 subtype B, whereas the reverse was true for subtype E. Identification and resolution of the problem of invalid runs markedly improved the quality of HIV-1 viral load testing. The variability observed between laboratories and between assays, even the most recent versions, dictates that monitoring of viral load in an individual should always be by the same laboratory and by the same assay. Results for an individual which differ by less than 0.5 log(10) HIV-1 RNA copy number/ml should not be considered clinically significant.
Assuntos
Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-1/fisiologia , Laboratórios/normas , Carga Viral , Austrália , Humanos , Controle de Qualidade , RNA Viral/sangue , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos TestesRESUMO
The role of Ca2+ in stimulation of aldosterone secretion (ASR) has been evaluated in vivo using conscious sheep with an adrenal cervical autotransplant. The calcium antagonists verapamil, nisoldipine, and lanthanum and the calcium ionophore BAY K 8644 were infused into the adrenal arterial supply before or concomitantly with angiotensin II. Nisoldipine reversed stimulation of ASR (n = 4) from 13.6 +/- 3.2 to 4.8 +/- 1.2 nmol/h (P less than 0.01; control 2.3 +/- 0.6 nmol/h), as did verapamil. Lanthanum had an intermediate effect. In contrast, pretreatment with nisoldipine (n = 5) did not affect the response to angiotensin II, with ASR being 3.8 +/- 0.9 nmol/h after nisoldipine alone and 12.8 +/- 1.3 nmol/h after nisoldipine plus angiotensin II. In response to graded infusion of angiotensin II, nisoldipine blunted (P less than 0.01) to a small degree the response at all doses of the peptide. Close adrenal arterial infusion of the ionophore BAY K 8644 similarly reversed stimulation of ASR by angiotensin II. It also blocked the initiation of response to the peptide. These data are consistent with the involvement of two pools of calcium in the zona glomerulosa response to angiotensin II, an intracellular pool that is primarily responsible for the initiation of response and a transmembrane extracellular pool that is primarily involved in the "sustained" response to angiotensin II.
Assuntos
Aldosterona/sangue , Angiotensina II/farmacologia , Cálcio/fisiologia , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Glândulas Suprarrenais/transplante , Animais , Hidrocortisona/metabolismo , Lantânio/farmacologia , Nifedipino/análogos & derivados , Nifedipino/farmacologia , Nisoldipino , Ovinos , Verapamil/farmacologiaRESUMO
1. To investigate a role for peptides derived from the precursor molecule pro-opiomelanocortin (POMC) on the control of aldosterone secretion (ASR), alpha-, beta-, gamma 1-, and gamma 2-melanocyte stimulating hormone (MSH), corticotropin-like intermediate lobe peptide (CLIP) or beta-endorphin were infused into the adrenal arterial supply of sheep with an adrenal cervical autotransplant. 2. None of the peptides had any significant effect on aldosterone secretion rate in Na replete, unstressed, conscious animals. In contrast, ACTH-stimulated ASR approximately twofold. 3. POMC-derived peptides other than ACTH appear to have little or no effect on the short-term control of aldosterone secretion in vivo, although a role in control and modulation of adrenal function over the longer term cannot be discounted.
Assuntos
Glândulas Suprarrenais/metabolismo , Aldosterona/metabolismo , Pró-Opiomelanocortina/farmacologia , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Endorfinas/metabolismo , Hidrocortisona/metabolismo , Hormônios Estimuladores de Melanócitos/metabolismo , OvinosRESUMO
The effect of angiotensin II (ANG II) on cytosolic free Ca2+ concentration ([Ca2+]i) was studied in cultured neonatal rat ventricular myocytes. [Ca2+]i was estimated in groups of one to three cells by dual-wavelength microfluorometry or in cell populations using conventional fluorometry. ANG II (10(-8) M) produced an acute short-lived increase over the control basal diastolic [Ca2+]i and increased the frequency of the [Ca2+]i transients. The amplitude of the [Ca2+]i transients was decreased to 64.4% of basal values. The effect of ANG II on [Ca2+]i was blocked by the selective AT1 receptor subtype antagonist Du Pont 753 but not by the AT2 antagonist PD 123319. Removal of extracellular Ca2+ or blockade of voltage-gated Ca2+ channels in cells cultured for 5-7 days abolished the [Ca2+]i transients, but only partially diminished the effect of ANG II on [Ca2+]i. Thapsigargin, an inhibitor of sarcoplasmic reticulum Ca(2+)-Mg(2+)-ATPase, reduced or abolished the [Ca2+]i response to ANG II. Phorbol 12-myristate 13-acetate (PMA), 10(-6) and 10(-7) M, also decreased the amplitude of the Ca2+ transients similar to ANG II. Pretreatment with 10(-6) M PMA or 10(-6) M 1-oleoyl-2-acetyl-glycerol (OAG) inhibited the initial rise in [Ca2+]i and the Ca2+ transients. Thus ANG II produces an acute rise in [Ca2+]i which is derived predominantly from sarcoplasmic reticulum intracellular stores. This acute effect is followed by a significant reduction in the amplitude for the Ca2+ transient and may be mediated by activation of protein kinase C.
Assuntos
Angiotensina II/fisiologia , Cálcio/metabolismo , Citosol/metabolismo , Miocárdio/metabolismo , Antagonistas de Receptores de Angiotensina , Animais , Animais Recém-Nascidos , Ligação Competitiva , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Células Cultivadas , Citofotometria , Contração Miocárdica , Miocárdio/citologia , Ratos , Ratos Endogâmicos , Receptores de Angiotensina/metabolismo , Terpenos , Acetato de Tetradecanoilforbol , TapsigarginaRESUMO
Conscious sheep whose sole adrenal gland had been transplanted to the neck to allow access to the adrenal vasculature were used to study the effect of calcium antagonists on aldosterone secretion. All animals were sodium depleted by uncompensated loss of parotid saliva. The drugs EDTA, verapamil, methoxyverapamil, nisoldipine, lanthanum, propylmethylenedioxyindene, and ryanodine were infused on separate occasions in three or four increasing dose levels. All infusions were made to produce known concentrations directly into the adrenal arterial blood supply. None of these infusions had any significant effect on aldosterone secretion rate, cortisol secretion rate, and little or no effect on plasma [Na], [K], or blood pressure. At high infusion rates some agents (verapamil, methoxyverapamil) caused tachycardia. In contrast, angiotensin II stimulation of aldosterone secretion is inhibited by both verapamil and nisoldipine. The data demonstrate that the sustained elevation of aldosterone secretion caused by sodium depletion is not dependent on a sustained alteration in transmembrane calcium flux. Furthermore, if circulating angiotensin II is the primary stimulus to aldosterone during sodium depletion, its mechanism of action appears to switch to one which is not dependent on calcium alone.