RESUMO
1. Both dietary magnesium depletion and potassium depletion (confirmed by tissue analysis) were induced in rats which were then compared with rats treated with chlorothiazide (250 mg/kg diet) and rats on a control synthetic diet. 2. Brain and muscle intracellular pH was measured by using a surface coil and [31P]-NMR to measure the chemical shift of inorganic phosphate. pH was also measured in isolated perfused hearts from control and magnesium-deficient rats. Intracellular magnesium status was assessed by measuring the chemical shift of beta-ATP in brain. 3. There was no evidence for magnesium deficiency in the chlorothiazide-treated rats on tissue analysis or on chemical shift of beta-ATP in brain. Both magnesium and potassium deficiency, but not chlorothiazide treatment, were associated with an extracellular alkalosis. 4. Magnesium deficiency led to an intracellular alkalosis in brain, muscle and heart. Chlorothiazide treatment led to an alkalosis in brain. Potassium deficiency was associated with a normal intracellular pH in brain and muscle. 5. Magnesium depletion and chlorothiazide treatment produce intracellular alkalosis by unknown mechanism(s).
Assuntos
Equilíbrio Ácido-Base , Encéfalo/metabolismo , Clorotiazida/farmacologia , Deficiência de Magnésio/metabolismo , Músculos/metabolismo , Miocárdio/metabolismo , Deficiência de Potássio/metabolismo , Equilíbrio Ácido-Base/efeitos dos fármacos , Alcalose/complicações , Alcalose/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Coração/efeitos dos fármacos , Técnicas In Vitro , Deficiência de Magnésio/complicações , Espectroscopia de Ressonância Magnética , Músculos/efeitos dos fármacos , Fósforo , Deficiência de Potássio/complicações , Ratos , Ratos EndogâmicosRESUMO
Renal intracellular pH (pHi) was measured in vivo from the chemical shift (sigma) of inorganic phosphate (Pi), obtained by 31P-nuclear magnetic resonance spectroscopy (NMR). pH was calculated from the difference between sigma Pi and sigma alpha-ATP. Changes of sigma Pi closely correlated with changes of sigma monophosphoesters; this supports the hypothesis that the pH determined from sigma Pi represents pHi. Renal pH in control rats was 7.39 +/- 0.04 (n = 8). This is higher than pHi of muscle and brain in vivo, suggesting that renal Na-H antiporter activity raises renal pHi. To examine the relationship between renal pH and ammoniagenesis, rats were subjected to acute (less than 24 h) and chronic (4-7 days) metabolic acidosis, acute (20 min) and chronic (6-8 days) respiratory acidosis, and dietary potassium depletion (7-21 days). Acute metabolic and respiratory acidosis produced acidification of renal pHi. Chronic metabolic acidosis (arterial blood pH, 7.26 +/- 0.02) lowered renal pHi to 7.30 +/- 0.02, but chronic respiratory acidosis (arterial blood pH, 7.30 +/- 0.05) was not associated with renal acidosis (pH, 7.40 +/- 0.04). At a similar level of blood pH, pHi was higher in chronic metabolic acidosis than in acute metabolic acidosis, suggesting an adaptive process that raises pHi. Potassium depletion (arterial blood pH, 7.44 +/- 0.05) was associated with a marked renal acidosis (renal pH, 7.17 +/- 0.02). There was a direct relationship between renal pH and cardiac K+. Rapid partial repletion with KCl (1 mmol) significantly increased renal pHi from 7.14 +/- 0.03 to 7.31 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Acidose/metabolismo , Hidrogênio/metabolismo , Membranas Intracelulares/metabolismo , Rim/metabolismo , Deficiência de Potássio/metabolismo , Acidose Respiratória/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Feminino , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Fósforo , Ratos , Ratos EndogâmicosRESUMO
In summary, MRS is a powerful tool for the noninvasive measurement of tissue metabolism and pH. 31P MRS measures high-energy phosphates and pH, 1H MRS measures carbon metabolism, and 14N detects nitrogenous compounds. Studies with perfused organs in experimental animals suggests that MRS has potential for noninvasive monitoring of the human kidney in health and disease. The production of large magnet systems which accommodate human subjects raises the possibility that MRS may be used for clinical diagnosis. There are several problems concerning the application of this technology to the investigation of human renal metabolism. Nevertheless, because this field is advancing so rapidly, it can be expected that within the next few years MRS will be used to study human kidneys in health and disease. Whether or not MRS proves to be a useful diagnostic tool in clinical medicine remains to be determined.
Assuntos
Nefropatias/diagnóstico , Rim/fisiologia , Espectroscopia de Ressonância Magnética , Injúria Renal Aguda/diagnóstico , Trifosfato de Adenosina/metabolismo , Animais , Humanos , Concentração de Íons de Hidrogênio , Testes de Função Renal , Neoplasias Renais/diagnóstico , Transplante de Rim , Nitrogênio , Perfusão , FósforoRESUMO
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)