H+ pump and Na+-H+ exchange in isolated single proximal tubules of spontaneously hypertensive rats

Abstract

To gain insight into the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR), we compared the maturation of the Na-independent H+ efflux and Na(+)-H+ exchange in microdissected superficial proximal cortical tubule (PCT) S1 and S2 segments of SHR and normotensive Wistar-Kyoto (WKY) rats. Isolated superfused PCT segments were loaded with 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein and incubated in nominally HCO3-free solution. We assessed Na-independent N-ethylmaleimide (NEM)-sensitive H+ efflux and Na-dependent H+ efflux by measuring the recovery rate of the intracellular pH following acid loading induced by prepulsing with NH4+. In young prehypertensive SHR the Na(+)-H+ exchange recovery rate in S1 at pH(i) 6.8 was significantly higher than in young WKY rats, whereas in adult rats no significant difference between the two strains could be observed. In S2 segments the Na(+)-H+ exchange recovery rate was similar between SHR and WKY rats for both age groups. In the young, no difference in the NEM-sensitive H+ efflux in S2 PCT was observed between the two strains. In contrast, in the adult, although the NEM-sensitive H+ efflux had increased profoundly with age for WKY rats, it remained markedly low in SHR. These studies indicate that apical Na+ reabsorption coupled with H+ efflux in the S1 segment is increased in the PCT of SHR, and demonstrate a marked impairment in the maturation of H+ pump activity in the S2 segment of the SHR compared with the normotensive strain. The impairment of these cell transport systems in the SHR may be relevant to the pathogenesis or maintenance of hypertension in this model.