SUMMARY1. The effect of peritubular PCO2 and pH changes within the physiological range on proximal tubular acidification ofnon-bicarbonate (phosphate) buffer was evaluated with and without carbonic anhydrase inhibition by stopped-flow microperfusion and Sb micro-electrode techniques.2. Luminal steady-state pH was reduced from 6-69 to 6-37 and H ion fluxes (JH+)increased from 0-63 to 1-57 nmol cm-2 s-1 by increasing capillary CO2 from 0 to 9-6 % at pH 7-2. 3. After acetazolamide a marked, although attenuated, effect ofCO2 on acidification was still observed; JH+ increased from 0-088 nmol cm-2 s-1 at 0 % CO2 to 0-78 at 9-6% CO2. Most of this effect can be explained by titration of luminal buffer by C02, uncatalysed CO2 hydration and H2CO3 recirculation.4. An increase in capillary CO2 reduced acidification half-times (t/2), which, according to an analogue circuit model, may be due to increased H ion access to the pump.5. Peritubular pH changes at 0 % CO2 also modified tubular acidification, increasing JH+ from 0-73 nmol cm-2 s-1 at pH 7-6 to 0 99 at pH 7 0. After acetazolamide, JH+ still increased from 0.11 nmol cm-2 s-1 at pH 7-6 to 0 57 at pH 7 0. 6. In conclusion, both peritubular C02 changes at constant pH and pH changes at 0 % C02 were effective to modify JH+, in the presence and absence of carbonic anhydrase activity. In the studied range, capillary C02 induced larger changes in JH+ than pH. The data show substrate (H ion) is a limiting factor for tubular H ion secretion.
The mechanism of tubular acidification was studied in proximal tubular acidification defect induced in rats by acute parenteral infusion of maleate (200 mg/kg), which causes diuresis and bicarbonaturia. Proximal tubular bicarbonate reabsorption and H+ ion secretion were determined by stopped-flow microperfusion and measurement of luminal pH by Sb microelectrodes. Stationary pH increased in proximal tubule from 6.78 to 7.25 and bicarbonate reabsorption decreased from 1.32 to 0.51 nmol/cm2 X s. In these segments, mean cell PD fell from -66.6 to -20.2 mV, while Jv as estimated by the Gertz technique fell to 15% of controls. A similar impairment of acidification was observed during luminal and capillary perfusion with phosphate Ringer's. Since H+-ion efflux from the lumen was not significantly increased and both acidification and alkalinization half-times (t/2) were increased, no evidence for an increase in passive permeability for H+/HCO3- was obtained. The increased t/2 found during luminal perfusion with acid phosphate indicates, according to an electrical analog model, a reduction in pump series conductance. These results show that maleate affects both proximal Na+ and H+ transport; this effect may be ascribed to impairment of sodium-dependent transport systems in the brush-border membrane.
Gostaria de agradecer a todos aqueles que contribuíram de forma decisiva para a concretização deste trabalho. Ao Prof.Dr. Kazuo Nishimoto, pela oportunidade de realizar este trabalho, pelo incentivo, pelo apoio e por me indicar os caminhos mais seguros nesta longa jornada. Ao Prof. Dr. Cheng Liang-Yee, que coorientou este trabalho, acompanhando cada passo do seu desenvolvimento, contribuindo com críticas precisas e sugestões valiosas. Ao Prof. Dr. José Luis Drummond Alves, pelas valiosas críticas e sugestões apresentadas durante o exame de qualificação. A todos os amigos e colegas do TPN que muito contribuíram de forma decisiva para a realização deste trabalho. À FUSP-Fundação de Apoio à Universidade de São Paulo, pela concessão da bolsa de doutorado e pelo apoio financeiro para a realização desta pesquisa. Ao Tanque de Provas Numérico (TPN) da Universidade de São Paulo, por colocar à disposição o cluster de computadores. Por último, manifesto um profundo reconhecimento à minha esposa Tânia e a minha filha Amanda, pelo apoio incondicional ao longo destes anos e, principalmente, por lidarem pacientemente com as constantes oscilações do meu humor, que balançavam ao ritmo da evolução dos meus esforços.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.