Proximal tubule Na transporter responses are the same during acute and chronic hypertension

Abstract

Acute hypertension in Sprague-Dawley rats (SD) provokes a decrease in renal proximal tubule (PT) salt and fluid reabsorption, redistribution of apical Na/H exchanger isoform 3 (NHE3) and Na-P(i) cotransporter type 2 (NaPi2) out of the brush border into higher density membranes, and inhibition of renal cortical Na-K-ATPase (NKA) activity (41). The aims of this study were to determine 1) whether an increase in arterial pressure affects distribution or activity of Na transporters in the spontaneously hypertensive rat (SHR) and 2) whether development of chronic hypertension in SHR leads to persistent adaptive changes in NHE3 and NaPi2 distribution and/or NKA activity. Renal cortex Na transporter protein density distributions and activities were compared by subcellular fractionation in 1) adult SHR with an acute increase or decrease in arterial pressure and 2) young SD (YSD) and young SHR (YSHR) vs. adult SD and SHR. In adult hypertensive SHR NHE3 was shifted to membranes of higher densities, analogous to SD with acute hypertension, and there were no further changes with a further increase or decrease in arterial pressure. There was no change in total pool size of NHE3 in cortex in YSHR vs. SHR. NHE3, NaPi2, megalin, NKA alpha-/beta-subunit, dipeptidyl peptidase IV (DPPIV), and villin distributions were the same in YSHR vs. YSD. NHE3, NaPi2, and megalin shifted to higher densities in adult SHR, but not SD, with age. Basolateral NKA and apical alkaline phosphatase activities were 40% greater in YSHR than YSD and decreased to SD levels in adults. We conclude that there are persistent changes in Na(+) transporter distributions and activity in response to chronic hypertension in SHR that mimic the responses to acute hypertension seen in SD rats and that elevated sodium pump activity per transporter in YSHR may contribute to the generation of hypertension.

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

“…An acute increase in BP leads to decreased renal phosphate reabsorption by inducing removal of Npt2a from the proximal tubule brush border membrane microvilli to subapical endosomes (53).…”

The Effects ofSyzygium aromaticum-Derived Oleanolic Acid on Kidney Function of Male Sprague–Dawley Rats and on Kidney and Liver Cell Lines

“…Na þ is mainly reabsorbed across the proximal tubular cell in a process mediated by proximal tubule apical NHE3 followed by uphill active extrusion via basolateral Na þ /K þ ATPase. 34,35 The literature on natriuretic hormones' actions in the proximal tubule, however, shows that transport inhibition is effected via parallel independent inhibition of apical NHE3 and basolateral Na þ /K þ ATPase. 36 We, therefore, speculate that OA inhibited apical NHE3 and basolateral Na þ /K þ ATPase accounting for Na þ excretion since NHE3 is a major Na þ transport pathway in the renal proximal tubule.…”

The Effect of Grape Seed Proanthocyanidin Extract (GSPE) on Urinary Sodium Excretion

“…Özellikle nefron boyunca gerçekleşen Na taşınması arteryel hipertansiyonun patogenezinde önemli yer almaktadır. Çeşitli deneysel çalışmalarda spontan hipertansif ratlarda proksimal tubuler Na-K ATP az aktivitesinde ve miktarında artış saptanmıştır [11]. Yine bazı deneysel çalışmalar-da spontan hipertansif ratlarda Na reabsorbsiyonunda artışa yol açan Na-K ATP az α1 subünitesinde artış saptanmıştır [12].…”