Dagher G, Sauterey C
Laboratoire de Physiologie Cellulaire, Collège de France, Paris.
J Hypertens. 1992 Sep;10(9):969-78.
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.
为深入了解自发性高血压大鼠（SHR）高血压的发病机制，我们比较了SHR和正常血压的Wistar - Kyoto（WKY）大鼠显微解剖的浅表近端皮质肾小管（PCT）S1和S2节段中不依赖钠的H⁺外流和Na⁺-H⁺交换的成熟情况。
将分离的灌注PCT节段用2'-7'-双羧乙基-5(6)-羧基荧光素加载，并在名义上无HCO₃的溶液中孵育。我们通过测量用NH₄⁺预脉冲诱导酸负荷后细胞内pH的恢复率来评估不依赖钠的N - 乙基马来酰亚胺（NEM）敏感的H⁺外流和依赖钠的H⁺外流。
在年轻的高血压前期SHR中，pH(i) 6.8时S1节段的Na⁺-H⁺交换恢复率显著高于年轻的WKY大鼠，而在成年大鼠中，两个品系之间未观察到显著差异。在S2节段，两个年龄组的SHR和WKY大鼠的Na⁺-H⁺交换恢复率相似。在年轻大鼠中，两个品系在S2 PCT中NEM敏感的H⁺外流没有差异。相反，在成年大鼠中，尽管WKY大鼠中NEM敏感的H⁺外流随年龄显著增加，但在SHR中仍明显较低。
这些研究表明，SHR的PCT中S1节段顶端Na⁺重吸收与H⁺外流耦合增加，并且与正常血压品系相比，SHR的S2节段中H⁺泵活性成熟存在明显损害。SHR中这些细胞转运系统的损害可能与该模型中高血压的发病机制或维持有关。
