Korean J Physiol Pharmacol.  1998 Oct;2(5):541-547.

Regulation of salt and volume transport along the nephron during acute systolic hypertension

Affiliations
  • 1Department of Physiology and Biophysics, University of Southern California School of Medicine, 1333 San Pablo Street, Los Angeles, CA 90033.

Abstract

DISCUSSION Acute regulation of sodium pump activity There is a burgeoning literature on mechanisms responsible for short term regulation of Na,K-ATPase activity (Aperia et al, 1996, 1994; Boron et al, 1997; Bertorello & Katz, 1993). Pathways linked to both generation of protein kinase C (PKC) and/or cyclic-AMP dependent protein kinase A are postulated to regulate Na,K-ATPase activity by changing the alpha catalytic subunit phosphorylation status. However, phosphorylation has been associated with both decreased activity (Aperia et al, 1994; Chibalin et al, 1995; Middleton et al, 1993; Satoh et al, 1993a, 1993b), and increased activity (Carranza et al, 1996a, 1996b), and no change in activity (Boron et al, 1997). There is also evidence that PKC causes a withdrawal of sodiuln pumps from the basolateral membranes even if there is mutation of the phosphorylation site (Boron et al, 1997). Proximal tubule Na,K-ATPase activity is also inhibited (whether directly or indirectly is not known) by activation of phospholipase A2 which stimulates production of arachidonate metabolites of cytochrome P-450 such as 20-HETE (Aperia et al, 1996; Nowicki et al, 1997; Ominato et al, 1996). Although the precise signaling mechanisms re main to be elucidated for the responses to altered blood pressure, our results indicate that the inhibition of the sodium pump activity in PT is due to structural modification of the pump itself or an associated regulator, rather than solely mediated by trafficking of active pumps to a new location, because the data demonstrate. significant changes in total ATPase activity that persist through membrane fractionation and phase partitioning, and our results implicate a role of cat P45O aa metabolism to 20-HETE in the response(Zhang et al, 1998) Altered natriuretic responses in hypertension As discussed in the introduction, an altered natriuretic response to an elevation in blood pressure is the hallmark of hypertension. The Spontaneously Hypertensive Rat (SHR)has numerous renal defects that could account for the development of hypertension. In regards to this project, the PT of SHR fail to respond normally to the natriuretic hormone dopamine (Kinoshita et al, 1989), and they have enhanced tubuloglomerular feedback (TGF) response (reviewed in Cowley & Roman, 1997). Our results indicate a distribution of apical sodium transportes in SHR is the same as in acutely hypertensive SD (Magyar et al, 1997), In summary, our findings to date suggest that the dynamic regulation of proximal tubule and loop of Henle sodium transport by fluctuations in blood pressure may be mediated by changes in sodium transporter characteristics at both the apical and basolateral membranes: 1) by reversible inhibition of basolateral Na,K-ATPase activity in the PT and activation in the TALH, and 2) relocation of a set of apical proteins, including NHE-3 and NaPi, consistent with redistribution to intermicrovillar cleft region and/or internalization to endosomal pools in the PT. The reciprocal modulation of Na,K-ATPase activity in PT and TALH contributes the driving force for activating TGF, while minimizing changes in delivery of salt and water to the hormone sensitive distal nephron.

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