RESUMEN
The present studies examined the effect of acute in vitro acidosis on chloride reabsorption in the rabbit cortical thick ascending limb of Henle (cTALH). Four protocols were used: hypercapnic acidosis; "isocapnic" peritubular acidosis (bath bicarbonate reduction to 10 mM); isocapnic luminal acidosis (luminal bicarbonate reduction to 10 mM); isocapnic peritubular acidosis in the absence of luminal potassium. Transepithelial voltage (VT) decreased during hypercapnic acidosis and increased with recovery. Chloride reabsorption (pmol X mm-1 X min-1) decreased from 50.3 +/- 8.4 to 15.7 +/- 5.6, then increased to 45.6 +/- 11.1 with recovery. Likewise, VT was decreased reversibly during isocapnic peritubular acidosis, and chloride reabsorption decreased by 60%. Chloride reabsorption was greater (28.3 +/- 3.6) when tubules were perfused at normal luminal pH than at an acidotic luminal pH (11.4 +/- 4.5; P less than 0.05). Luminal potassium removal reduced chloride transport, and acidosis had no significant additional effect. Decreased chloride reabsorption in the cTALH during acidosis could contribute to the chloruresis associated with systemic acidosis. The symmetrical nature of this effect suggests that acidosis inhibits chloride reabsorption through an effect on cytosolic pH.
Asunto(s)
Acidosis/metabolismo , Cloruros/metabolismo , Corteza Renal/metabolismo , Túbulos Renales/metabolismo , Asa de la Nefrona/metabolismo , Animales , Transporte Biológico Activo , Femenino , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Cinética , Potenciales de la Membrana , Perfusión , ConejosRESUMEN
We examined the hypothesis that proton-potassium-activated adenosine triphosphatase (H-K-ATPase) mediates K absorption and acidification in the inner stripe of the outer medullary collecting duct (OMCDi). Rabbits were fed a low-K diet (0.55% K) for 7-14 d because we have demonstrated previously that this low-K diet stimulates K-absorptive flux by the OMCDi. Proton secretion was measured as net total CO2 flux (JTCO2) by microcalorimetry. After basal collections, either vehicle or an inhibitor of gastric H-K-ATPase, omeprazole (0.1 mM), was added to the perfusate during the second period. Addition of vehicle to the perfusate changed neither the transepithelial voltage (VT, in millivolts) nor the JTCO2. In contrast, the addition of omeprazole (0.1 mM) to the perfusate abolished JTCO2 (from 14.5 +/- 5.6 to -0.1 +/- 3.1 pmol.mm-1.min-1) without significantly affecting VT. In additional experiments, in 16 tubules there was significant net K absorption (JK) of 5.0 +/- 1.0 pmol.mm-1.min-1 during the basal period, which exceeded the rate of K absorption that could be attributed to a paracellular voltage-mediated pathway (JKP = 1.0 +/- 0.4 pmol.mm-1.min-1, P less than 0.01). Administration of vehicle did not significantly affect either VT or JK. However, omeprazole abolished JK (from 5.1 +/- 1.0 to 0.1 +/- 2.5 pmol.mm-1.min-1) without affecting VT or JNa. The present results demonstrate that the OMCDi possesses an active, omeprazole-sensitive acidification and K-absorptive mechanism. These findings are consistent with the presence of H-K-ATPase activity in this nephron segment.
Asunto(s)
Túbulos Renales Colectores/metabolismo , Túbulos Renales/metabolismo , Potasio/metabolismo , Protones , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Absorción , Animales , Bicarbonatos/metabolismo , Femenino , Técnicas In Vitro , Omeprazol/farmacología , Conejos , Sodio/metabolismo , Estómago/enzimologíaRESUMEN
Addisonian patients can maintain potassium homeostasis despite the absence of mineralocorticoid. The present in vitro microperfusion studies examine what role the cortical collecting tubule might play in this process. All studies were performed on tubules harvested from adrenalectomized rabbits, which were maintained on 0.15 M NaCl drinking water and dexamethasone 50 mug/d. Perfusion and bath solutions were symmetrical Ringer's bicarbonate with [K] of 5 meq/liter. Initial studies on cortical collecting tubules from adrenalectomized animals ingesting a high potassium chow (9 meq K/kg body wt) demonstrated net potassium secretion against an electrochemical gradient (mean collected fluid [K] 16.5+/-2.6 meq/liter with an observed transepithelial voltage of -6.3+/-4.1 mV; predicted voltage for passive distribution of potassium being -28.2 mV). To examine whether this active potassium secretion could be modulated by dietary potassium, independent of mineralocorticoid, two diets identical in all respects except for potassium content were formulated. Potassium secretion was compared in cortical collecting tubules harvested from adrenalectomized animals on low (0.1 meq K) and high (10 meq K) potassium intake. Mean net potassium secretion by cortical collecting tubules was 2.02+/-0.54 peq mm(-1) min(-1) in the low potassium diet group and 5.34+/-.74 peq.mm(-1).min(-1) in the high potassium group. The mean transepithelial voltages of the collecting tubules did not differ between the two dietary groups. While net Na reabsorption was significantly greater in tubules from the high K group, this could not account for the differences in K secretion. These data demonstrate that: (a) the cortical collecting tubule can actively secrete potassium and that the magnitude of this potassium secretion correlates with potassium intake; (b) this active potassium secretory process in independent of mineralocorticoid. These findings support the hypothesis that the cortical collecting tubule may contribute to K homeostasis in Addison's disease.
Asunto(s)
Corteza Renal/metabolismo , Túbulos Renales Colectores/metabolismo , Túbulos Renales/metabolismo , Mineralocorticoides/fisiología , Potasio/metabolismo , Enfermedad de Addison/metabolismo , Adrenalectomía , Animales , Transporte Biológico Activo , Dieta , Femenino , Homeostasis , Potenciales de la Membrana , Potasio/sangre , Potasio/orina , ConejosRESUMEN
AIM: Increasing evidence demonstrates that circadian clock proteins are important regulators of physiological functions including blood pressure. An established risk factor for developing cardiovascular disease is the absence of a blood pressure dip during the inactive period. The goal of the present study was to determine the effects of a high salt diet plus mineralocorticoid on PER1-mediated blood pressure regulation in a salt-resistant, normotensive mouse model, C57BL/6J. METHODS: Blood pressure was measured using radiotelemetry. After control diet, wild-type (WT) and Per1 (KO) knockout mice were given a high salt diet (4% NaCl) and the long-acting mineralocorticoid deoxycorticosterone pivalate. Blood pressure and activity rhythms were analysed to evaluate changes over time. RESULTS: Blood pressure in WT mice was not affected by a high salt diet plus mineralocorticoid. In contrast, Per1 KO mice exhibited significantly increased mean arterial pressure (MAP) in response to a high salt diet plus mineralocorticoid. The inactive/active phase ratio of MAP in WT mice was unchanged by high salt plus mineralocorticoid treatment. Importantly, this treatment caused Per1 KO mice to lose the expected decrease or 'dip' in blood pressure during the inactive compared to the active phase. CONCLUSION: Loss of PER1 increased sensitivity to the high salt plus mineralocorticoid treatment. It also resulted in a non-dipper phenotype in this model of salt-sensitive hypertension and provides a unique model of non-dipping. Together, these data support an important role for the circadian clock protein PER1 in the modulation of blood pressure in a high salt/mineralocorticoid model of hypertension.
Asunto(s)
Hipertensión/metabolismo , Hipertensión/fisiopatología , Proteínas Circadianas Period/metabolismo , Animales , Presión Sanguínea/fisiología , Desoxicorticosterona/análogos & derivados , Desoxicorticosterona/farmacología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Hipertensión/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mineralocorticoides/farmacología , Proteínas Circadianas Period/deficiencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Cloruro de Sodio Dietético/farmacologíaRESUMEN
Renovascular hypertension is potentially curable but of low prevalence. A previous retrospective study has demonstrated the use of a potentiated increase in plasma renin activity after captopril administration as a diagnostic test for renovascular hypertension; this requires two blood samples for plasma renin activity determination and three inclusive criteria for a positive test result. We applied this test prospectively to screen 100 hypertensive patients for renovascular hypertension. We evaluated 29 patients with renovascular hypertension; the remainder were diagnosed as having essential hypertension. In our patient population, a postcaptopril plasma renin activity of 5.7 ng of angiotensin per milliliter per hour (ngAl.mL-1.h-1) or greater had a 100% sensitivity and an 80% specificity for renovascular hypertension. An absolute increase in plasma renin activity with captopril of 4.7 ngAl.mL-1.h-1 or greater had a lower sensitivity of 90% and a specificity of 87%, whereas a fractional increase in plasma renin activity after captopril of 150% or higher had the lowest sensitivity of 69% and a specificity of 86%. A subgroup analysis of 38 patients who were receiving diuretic therapy demonstrated that the test sensitivity was unchanged but the specificity was reduced. In conclusion, a single postcaptopril plasma renin activity value of 5.7 ngAl.mL-1.h-1 or greater is a simplified screening test for renovascular hypertension, with excellent sensitivity and acceptable specificity. This test is well tolerated, inexpensive, and easy to perform.
Asunto(s)
Captopril , Hipertensión Renovascular/diagnóstico , Diuréticos/uso terapéutico , Humanos , Hipertensión/diagnóstico , Hipertensión Renovascular/epidemiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Renina/sangre , Sensibilidad y EspecificidadRESUMEN
The outer medullary collecting duct (OMCD) produces high rates of proton secretion, and previous data show a significant role for an H+,K+-ATPase in luminal acidification. This mechanism of acidification requires proton secretion to occur in exchange for potassium absorption. Because net transport of potassium is small in the OMCD, pathways for potassium secretion would appear essential to explain the contribution of an H+,K+-ATPase under potassium-replete conditions. A significant issue is whether a potassium exit pathway (i.e., cation channel) is present at the apical and/or the basolateral membrane. In this report, using patch-clamp techniques to examine single channel conductances from the native rabbit OMCD, we show that the apical membrane has potassium permeable cation channels.
Asunto(s)
ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Túbulos Renales Colectores/metabolismo , Potasio/metabolismo , Animales , Membrana Celular/fisiología , Células Cultivadas , Homeostasis/fisiología , Transporte Iónico/fisiología , Médula Renal , Túbulos Renales Colectores/citología , Técnicas de Placa-Clamp , Bombas de Protones/fisiología , Conejos , Sensibilidad y EspecificidadRESUMEN
The pharmacological properties of H+,K+-ATPase activity described in the kidney were not necessarily consistent with the properties of the well-characterized gastric H+,K+-ATPase. Recent molecular biology experiments suggest that renal H+,K+-ATPase activity may be the product of several closely related P-type ATPases. At least 3 different pumps containing the HKalpha1, HKalpha2a, and HKalpha2c subunits have been detected in rabbit kidney. The current view is that these HKalpha subunits arose through gene duplication early in evolution and the proteins evolved their differing activities over time. The HKbeta protein associates with HKalpha1 in gastric tissues and is the likely mate for the HKalpha1 subunit in renal tissues. Three distinct beta subunits have been implicated as possible partners for the HKalpha2 subunits, but it remains to be determined which beta subunit predominantly associates with the HKalpha2 subunits in vivo. Sequence analysis suggests the beta subunit was constrained by size and shape of the protein rather than specific amino acid content during the course of evolution. Multiple H+,K+-ATPases in the kidney may be an important adaptation providing redundancy for the essential physiological function of maintaining ionic balance.
Asunto(s)
ATPasa Intercambiadora de Hidrógeno-Potásio/genética , Túbulos Renales Colectores/enzimología , Secuencia de Aminoácidos , Animales , ADN Complementario/análisis , Perros , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Humanos , Transporte Iónico/fisiología , Túbulos Renales Colectores/fisiología , Ratones , Biología Molecular , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Conejos , Ratas , Especificidad de la Especie , Equilibrio HidroelectrolíticoRESUMEN
Medical research has been demonstrated to increase the quality of life for all Americans and to be a sound investment with clear financial savings. However, academic health centers, which are the major source of medical research, have experienced continued erosion of their financial base of support. The author reviews some of the elements which have precipitated the current crisis for many academic health centers and proposes short- and long-term goals that should be endorsed by academic medical societies as a means of reducing these institutions' financial dependence on clinical income and restoring to them their primary social mission: to train the highest caliber of practicing physicians and to be centers of fundamental, not technological, research. Such research has been demonstrated to reduce, not increase, health care costs. Academic medical societies must work together to educate the public and Congress about the needs of academic health care centers, and to provide a cohesive and constructive set of practical recommendations that can strengthen their future financial stability.
Asunto(s)
Centros Médicos Académicos/economía , Atención a la Salud/tendencias , Investigación , Sociedades Médicas , Centros Médicos Académicos/organización & administración , Economía Hospitalaria/tendencias , Economía Médica/tendencias , Educación de Postgrado en Medicina/economía , Educación de Postgrado en Medicina/estadística & datos numéricos , Programas Controlados de Atención en Salud , Medicina/estadística & datos numéricos , Investigación/economía , Apoyo a la Investigación como Asunto/tendencias , Sociedades Médicas/organización & administración , EspecializaciónRESUMEN
A 67-year-old white woman developed severe nausea, vomiting, diffuse abdominal cramping pain, and blurred vision followed by a syncopal episode after taking 1 tablet of quinine for leg cramps. Examination was significant for fever, elevated blood pressure, and confusion without any focal neurological deficits. Laboratory studies showed markedly elevated liver enzymes, elevated lactate dehydrogenase, anemia, thrombocytopenia, and acute renal failure. Peripheral smear showed many schistocytes and burr cells. She later recalled taking quinine more than 40 years before while on a trip to the Philippines. The patient was treated with 7 sessions of plasmapheresis with a rapid normalization of her hematological parameters. Three weeks of dialysis support were required before return of renal function to baseline. Re-exposure to quinine can cause a rapid onset of hemolytic uremic syndrome-like syndrome. We are not aware of any cases of hemolytic uremic syndrome-thrombotic thrombocytopenic purpura in response to re-exposure to a single tablet of the drug 40 years after first use.
Asunto(s)
Síndrome Hemolítico-Urémico/inducido químicamente , Síndrome Hemolítico-Urémico/diagnóstico , Púrpura Trombocitopénica Trombótica/inducido químicamente , Púrpura Trombocitopénica Trombótica/diagnóstico , Quinina/efectos adversos , Anciano , Diagnóstico Diferencial , Femenino , Síndrome Hemolítico-Urémico/sangre , Humanos , Púrpura Trombocitopénica Trombótica/sangreRESUMEN
Proteinuria may be associated with a renal or systemic disease, or it may be isolated. The latter occurs in asymptomatic patients without evidence of any disease or abnormality of the urine sediment. Isolated proteinuria may be subdivided into two broad groups: (1) benign forms, with a favorable-to-excellent prognosis and (2) persistent forms, some of which have a worrisome prognosis. Functional proteinuria may occur in disorders with altered renal hemodynamics, usually resolves, and is not associated with progressive renal disease. Idiopathic transient proteinuria is typically discovered on routine screening and usually disappears on subsequent testing. In idiopathic intermittent proteinuria, a significant number (50%) of urine samples exhibit abnormal rates of protein excretion. Although structural abnormalities may be observed on renal biopsy, progressive renal insufficiency is unusual. In orthostatic proteinuria, the rate of protein excretion completely normalizes in the recumbent position. Long-term studies show this to be a benign condition. In persistent isolated proteinuria, at least 80% of random urine samples exhibit abnormal protein excretion. This represents a heterogeneous group, but a significant proportion of these patients have prominent renal pathologic findings and progress to serious renal disease. Proteinuria with significant renal disease may be non-nephrotic or nephrotic range. The former does not exclude glomerular disease, but tubulointerstitial or vascular disorders are also likely when proteinuria is less than 2 g/24 hours. Patients with nephrotic-range proteinuria generally have a glomerular disorder. Distinction between benign and more ominous forms of proteinuria requires careful evaluation.
Asunto(s)
Riñón/metabolismo , Riñón/patología , Proteinuria/diagnóstico , Proteinuria/etiología , Glomerulonefritis Membranosa/metabolismo , Glomerulonefritis Membranosa/patología , Humanos , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Nefrosis/clasificación , Nefrosis/complicaciones , Nefrosis/metabolismo , Nefrosis/patología , Postura , Pronóstico , Proteinuria/metabolismo , Proteinuria/patologíaRESUMEN
Nonpharmacologic treatment currently is recognized as an important part in the treatment of hypertension, and the role of dietary potassium intake in blood pressure (BP) control is becoming quite evident. Clinical studies have examined the mechanism by which hypokalemia can increase BP and the benefit of a large potassium intake on BP control. Epidemiologic data suggest that potassium intake and BP are correlated inversely. In normotensive subjects, those who are salt sensitive or who have a family history of hypertension appear to benefit most from the hypotensive effects of potassium supplementation. The greatest hypotensive effect of potassium supplementation occurs in patients with severe hypertension. This effect is pronounced with prolonged potassium supplementation. The antihypertensive effect of increased potassium intake appears to be mediated by several factors, which include enhancing natriuresis, modulating baroreflex sensitivity, direct vasodilation, or lowering cardiovascular reactivity to norepinephrine or angiotensin II. Potassium repletion in patients with diuretic-induced hypokalemia improves BP control. An increase in potassium intake should be included in the nonpharmacologic management of patients with uncomplicated hypertension.
Asunto(s)
Presión Sanguínea , Deficiencia de Potasio/tratamiento farmacológico , Deficiencia de Potasio/fisiopatología , Potasio/administración & dosificación , Antihipertensivos , Dieta , Humanos , Potasio/efectos adversosRESUMEN
Bacillary angiomatosis is a newly characterized infectious disease occurring mainly in patients with AIDS. Most patients have cutaneous angiomatosis lesions resembling Kaposi's sarcoma or pyogenic granuloma. Although the disease may be life-threatening if not treated, it is curable with appropriate antibiotic therapy. A patient had a fever, nightsweats, abdominal pain, pleural effusions, and asymmetric peripheral lymphadenopathy. Computed tomography of the chest and abdomen revealed a unique pattern of enhancement of lymph nodes that, to this research team's knowledge, has not been reported previously with this condition. Appropriate antibiotic therapy resulted in a complete resolution of the disease. Included is a discussion of the clinical presentation, etiology, histology, and treatment of bacillary angiomatosis.
Asunto(s)
Angiomatosis Bacilar/complicaciones , Enfermedades Linfáticas/complicaciones , Adulto , Angiomatosis Bacilar/diagnóstico por imagen , Humanos , Enfermedades Linfáticas/diagnóstico por imagen , Masculino , Radiografía Abdominal , Radiografía Torácica , Tomografía Computarizada por Rayos XRESUMEN
Control of gene transcription is a major regulatory determinant for function of the endothelin pathway. Epigenetic mechanisms act on tissue-specific gene expression during development and in response to physiological stimuli. Most of the limited evidence available on epigenetic regulation of the endothelin pathway focuses on the EDN1 and EDNRB genes. Examination of whole genome databases suggests that both genes are influenced by histone modifications and DNA methylation. This interpretation is supported by studies directed at detecting epigenetic action on the two genes. The clearest illustration of epigenetic factors altering endothelin signalling is DNA methylation-associated EDNRB silencing during tumourigenesis. This review summarizes our current understanding of epigenetic regulation of the endothelin pathway genes. LINKED ARTICLES This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168.issue-1.
Asunto(s)
Endotelinas/genética , Animales , Metilación de ADN , Epigénesis Genética , Histonas/metabolismo , HumanosRESUMEN
Dietary K intake has been shown to influence solute flux in the cortical collecting duct (CCD). We recently observed active Cl secretion by the CCD when rabbits were fed a K-rich diet. The present studies examined two different methods of K loading (KHCO3 or KCl) on net Cl flux (JNet Cl), active Cl flux (JA Cl), and passive Cl flux (JP Cl) by the rabbit CCD. These two methods of K loading were compared with a low-K diet (control or NaHCO3 diet) that had the same anion composition as the KHCO3 diet (Na for K substitution). In the low-K group there was neither significant net Cl transport nor active Cl secretion. Increasing dietary K content (KHCO3 group) resulted in significant net Cl secretion (JNet Cl = -26.3 +/- 9.3 pmol.mm-1.min-1). Moreover, K secretion was significantly greater (23.8 +/- 4.3 pmol.mm-1.min-1) and transepithelial voltage (VT) was more lumen negative (-14.8 +/- 5.9 mV) compared with the low-K group (P less than 0.05). Consequently, there was both significant passive Cl absorption and significant active Cl secretion. In the KCl group there was significant net Cl absorption (JNet Cl = 17.2 +/- 5.1 pmol.mm-1.min-1, P less than 0.05 vs. low-K diet). However, Na absorption significantly exceeded JNet Cl (JNet Na = 42.0 +/- 7.2 pmol.mm-1.min-1, P less than 0.01), and this group also exhibited the most lumen-negative voltage (VT = -35.4 +/- 5.4 mV).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Túbulos Renales Colectores/metabolismo , Túbulos Renales/metabolismo , Compuestos de Potasio , Animales , Bicarbonatos/administración & dosificación , Transporte Biológico , Transporte Biológico Activo , Cloruros/metabolismo , Dieta , Electrofisiología , Epitelio/fisiología , Femenino , Corteza Renal , Túbulos Renales Colectores/fisiología , Potasio/metabolismo , Cloruro de Potasio/administración & dosificación , Conejos , Sodio/administración & dosificación , Sodio/metabolismo , Bicarbonato de SodioRESUMEN
We have demonstrated previously active Cl and K secretion by the cortical collecting tubule (CCT). The aim of these studies was to determine whether a component of Cl and K secretion is coupled. Such coupling has been observed in the rat distal nephron but K secretion in the rabbit CCT is believed to be strictly conductive. We measured the rate of K secretion in three protocols. In the first, bath bumetanide did not affect K secretion but K secretion (-JK; in pmol.mm-1.min-1) decreased from 12.7 +/- 2.2 to 8.28 +/- 1.2 when gluconate replaced bath Cl (P less than 0.01), whereas transepithelial voltage (VT) and lumen-to-bath 22Na flux (JNal----b) were unchanged. In the second, bath Cl removal stimulated significant K absorption (JK, from -0.19 +/- 0.97 to 2.03 +/- 0.57) only in the presence of a lumen-to-bath Cl gradient (Na-free perfusate). This identical maneuver had no effect on JK in the absence of luminal Cl (NaCl-free perfusate). In the third, reducing luminal [Cl] from 112 to 5 mM stimulated K secretion from 13.6 +/- 3.1 to 20.1 +/- 3.2 (P less than 0.01) without affecting VT or net Na transport. We conclude the following: the CCT possesses a Cl-dependent K secretory mechanism that can be influenced by the transepithelial Cl gradient independent of VT and JNal----b. Reducing luminal [Cl] stimulates K secretion and K secretion can be reversed to K absorption by reversal of the ambient Cl gradient. These data imply a coupling between a component of K and Cl fluxes, consistent with the presence of KCl cotransport in the rabbit CCT.
Asunto(s)
Proteínas Portadoras/metabolismo , Cloruros/metabolismo , Túbulos Renales Colectores/metabolismo , Túbulos Renales/metabolismo , Potasio/metabolismo , Animales , Transporte Biológico Activo , Bumetanida/farmacología , Femenino , Proteínas de la Membrana/metabolismo , Conejos , Simportadores de Cloruro de Sodio-PotasioRESUMEN
These studies examine the effect of dietary K content on the rate efflux coefficient (KK) assessed both isotopically (42K) and by net K flux in segments dissected from the inner stripe of the outer medullary collecting tubule (MCT). Female New Zealand White rabbits were given either a K-replete diet (KCl diet) or one of two K-restricted diets with similar (142 meq K/kg diet) K content [basic (Na-deplete) diet or NaCl (Na-replete) diet]. After 7 days, renal K excretion (mmol/24 h) varied with K intake: KCl diet, 13.8 +/- 3.0; basic diet, 4.36 +/- 0.12; NaCl diet, 4.13 +/- 0.48. To determine whether alterations in KK of MCT could contribute to these changes in urinary K excretion, the MCT from the three groups of rabbits was perfused in vitro and volume reabsorption and KK were measured. The KK of tubules from the K-replete control group (KCl diet) was 82 +/- 14 nm/s but was significantly greater in tubules from either K-restricted group: 224 +/- 49 nm/s (basic diet group) or 193 +/- 34 nm/s (NaCl diet group). Net K flux in the presence of a 15 mM lumen-to-bath K gradient confirmed a significantly greater K reabsorptive flux and net rate coefficient in either K-restricted group (KNetK = 179 +/- 77 nm/s for the NaCl diet, KNetK = 170 +/- 27 nm/s for the basic diet) than the K-replete control group (KNetK = 12.0 +/- 18 nm/s for the KCl diet).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Túbulos Renales Colectores/metabolismo , Túbulos Renales/metabolismo , Potasio/farmacocinética , Aldosterona/sangre , Algoritmos , Animales , Transporte Biológico , Dieta , Femenino , Músculos/metabolismo , Permeabilidad , Potasio/administración & dosificación , Conejos , Cloruro de Sodio/administración & dosificaciónRESUMEN
In various epithelia K and Cl transport are molecularly coupled and KCl cotransport is dependent on the Na-K pump. The present study examines 1) the effect of a bath-to-lumen Cl gradient on K secretion during active Na transport and 2) the effect of basolateral ouabain on K secretion and Na absorption in the presence and the absence of a bath-to-lumen Cl gradient. Under symmetrical conditions there was significant K secretion (JK = -24.0 +/- 3.9 pmol.mm-1.min-1) and Cl secretion (JCl = -15.7 +/- 3.7 pmol.mm-1.min-1). Transepithelial voltage (VT) was significantly lumen negative (-25.3 +/- 5.9 mV), and Cl secretion occurred against its electrochemical gradient by a transcellular mechanism. Increasing bath [Cl] did not hyperpolarize VT; in fact there was a tendency for VT to depolarize and K secretion was not stimulated. However, ouabain significantly inhibited active Cl secretion and net Na absorption both in the presence and absence of a bath-to-lumen Cl gradient. Furthermore, ouabain totally inhibited K secretion in the absence of external ion gradients but inhibited K secretion by only 50% in the presence of a bath-to-lumen Cl gradient. This ouabain-insensitive K secretion exhibited a codependence on Cl secretion. Thus K secretion may occur passively, utilizing Cl movement down its electrochemical gradient when active Na transport is inhibited by ouabain. The results are compatible with the presence of a Cl-linked K-secretory process in the rabbit CCT.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Cloruros/farmacología , Corteza Renal/fisiología , Túbulos Renales Colectores/fisiología , Túbulos Renales/fisiología , Ouabaína/farmacología , Potasio/metabolismo , Animales , Cloruros/metabolismo , Epitelio/fisiología , Femenino , Corteza Renal/efectos de los fármacos , Túbulos Renales Colectores/efectos de los fármacos , Cinética , Matemática , Modelos Teóricos , Conejos , Valores de Referencia , Sodio/metabolismoRESUMEN
The present study examined the effect of sodium transport inhibition by amiloride, ouabain, and luminal sodium removal on potassium secretion in isolated cortical collecting tubules from adrenalectomized and DOCA-stimulated rabbits. Collecting tubules from adrenalectomized rabbits had a mean potassium secretion of 3.62 +/- 0.37 pmoles X mm-1 X min-1, which significantly decreased to 1.52 +/- 0.21 pmoles X mm-1 X min-1 after addition of amiloride, but no additional effect was observed after the addition of ouabain. The transepithelial voltage (VT) became less positive after exposure to amiloride. Cortical collecting tubules from DOCA-treated animals exhibited significantly greater potassium secretion (28.6 +/- 9.4 pmoles X mm-1 X mm-1). Amiloride totally inhibited potassium secretion, and VT reversed polarity in these tubules. In tubules from adrenalectomized rabbits the removal of luminal sodium inhibited potassium secretion by approximately 44% but had no effect on VT. There remained, however, a substantial amount of potassium secretion in the absence of transepithelial sodium flux. Thus, potassium secretion in the cortical collecting tubule is highly dependent on sodium reabsorption under conditions of mineralocorticoid stimulation but significantly less so in adrenalectomized animals. Potassium secretion in the cortical collecting tubule of adrenalectomized rabbits is inhibited independent of VT and occurs, in part, by an apparent electroneutral process. Chronic exposure to mineralocorticoids appears to stimulate electrogenic sodium reabsorption and potassium secretion.
Asunto(s)
Amilorida/farmacología , Canales Iónicos/fisiología , Túbulos Renales Colectores/metabolismo , Túbulos Renales/metabolismo , Ouabaína/farmacología , Potasio/metabolismo , Pirazinas/farmacología , Glándulas Suprarrenales/fisiología , Adrenalectomía , Animales , Transporte Biológico Activo/efectos de los fármacos , Desoxicorticosterona/farmacología , Femenino , Canales Iónicos/efectos de los fármacos , Túbulos Renales Colectores/efectos de los fármacos , Conejos , Sodio/metabolismo , Estimulación QuímicaRESUMEN
Previous studies have shown that Na-K-ATPase activity in the cortical collecting tubule of the rabbit increases significantly with mineralocorticoid stimulation and decreases significantly with adrenalectomy. The present study examined the effects of 10(-4) M ouabain on K secretion in the isolated perfused cortical collecting tubules from normal, adrenalectomized, and mineralocorticoid-stimulated animals. Potassium secretion was similar in the tubules from adrenalectomized (3.42 +/- 0.53 pmol X mm-1 X min-1) and from normal rabbits (3.38 +/- 0.36 pmol X mm-1 X min-1). K secretion was greater (15.1 +/- 3.0 pmol X mm-1 X min-1) in tubules from animals receiving 11-deoxycorticosterone acetate (DOCA). Ouabain inhibition of K secretion was 74% for the adrenalectomized group, 86% for the normal group, and 98% for the DOCA-treated group. The degree of inhibition was statistically equivalent among the three groups and not statistically different from complete inhibition of K secretion. Ouabain had no effect on the lumen-positive transepithelial voltage of the cortical collecting tubules from adrenalectomized rabbits but reduced the lumen-negative voltage in tubules from normal rabbits and reversed the polarity of the transepithelial voltage in cortical collecting tubules from DOCA-treated animals. Thus adrenal mineralocorticoids may be necessary for maximal K secretion by the cortical collecting tubule, but they are not essential to maintain K secretion during "normal" K intake. In all groups K secretion is totally dependent on Na-K-ATPase. The lumen-positive transepithelial voltage from DOCA-treated animals after addition of ouabain suggests an additional effect of mineralocorticoid to stimulate secretion of cations (protons) or reabsorption of anions.