In June’s edition of JASN Jacques et al. highlighted the emerging importance of therole of chloride in the pathogenesis of hypertension.
Their group developed a mouse model that over expressed the protein pendrin in
the aldosterone-sensitive region of the distal tubule. These mice developed
hypertension that was attributed to increased NaCl absorption driven by over
expression and increased activity of the pendrin chloride exchanger.
Pendrin was first described as a chloride channel in the
kidney in the early 2000s. Pendrin is a chloride-bicarbonate exchange protein that
facilitates the electroneutral movement of chloride to the intracellular space
and bicarbonate to the extracellular space or urinary space. This channel is
also found in the thyroid and inner ear and is the gene that causes Pendreds syndrom.
kidney in the early 2000s. Pendrin is a chloride-bicarbonate exchange protein that
facilitates the electroneutral movement of chloride to the intracellular space
and bicarbonate to the extracellular space or urinary space. This channel is
also found in the thyroid and inner ear and is the gene that causes Pendreds syndrom.
It is now widely accepted that the pressor effects of salt
(NaCl) are dependent on Na as the major determinant of intravascular volume and
thus hypertension. It has also been demonstrated that for Na to mediate a
hypertensive effect, it needs to be in the form of NaCl (Berghoff and Geraci,
Intern Med J 56:395-397). In their study, Berghoff and Geraci showed that subjects
on a high NaCl diet but not on a high NaBicarbonate diet developed hypertension.
These experiments have been reproduced in human and animal models. Interestingly,
hypertensive and normotensive subjects switched from a NaCl diet to an
equimolar NaBicarbonate diet experienced a decrease in blood pressure.
(NaCl) are dependent on Na as the major determinant of intravascular volume and
thus hypertension. It has also been demonstrated that for Na to mediate a
hypertensive effect, it needs to be in the form of NaCl (Berghoff and Geraci,
Intern Med J 56:395-397). In their study, Berghoff and Geraci showed that subjects
on a high NaCl diet but not on a high NaBicarbonate diet developed hypertension.
These experiments have been reproduced in human and animal models. Interestingly,
hypertensive and normotensive subjects switched from a NaCl diet to an
equimolar NaBicarbonate diet experienced a decrease in blood pressure.
Pendrin is normally found in the type B Intercalated cells
of the aldosterone region of the nephron. Recently published studies by the
same group suggest that pendrin can also work in tandem with the Na-dependent chloride/bicarbonate
exchanger (this is a different channel to pendrin and is also found in the CCD)
resulting in electroneutral NaCl absorption and that this process is thiazide
sensitive.
of the aldosterone region of the nephron. Recently published studies by the
same group suggest that pendrin can also work in tandem with the Na-dependent chloride/bicarbonate
exchanger (this is a different channel to pendrin and is also found in the CCD)
resulting in electroneutral NaCl absorption and that this process is thiazide
sensitive.
In JASNs June edition, the Jacques group showed that pendrin mediates
chloride absorption distally and that this is the driving force for Na
absorption distally either through the ENaC and/or Ndcbe channels. The
significance of their findings are that 1) chloride is required for NaCl
absorption in ‘salt sensitive’ hypertension and that 2) pendrin is the channel
that facilitates the absorption of chloride.
chloride absorption distally and that this is the driving force for Na
absorption distally either through the ENaC and/or Ndcbe channels. The
significance of their findings are that 1) chloride is required for NaCl
absorption in ‘salt sensitive’ hypertension and that 2) pendrin is the channel
that facilitates the absorption of chloride.
On the basis of this paper and other papers showing similar
findings with regard to Pendrin’s role in NaCl balance the authors suggest their
work solidifies the concept of chloride-sensitive hypertension.
findings with regard to Pendrin’s role in NaCl balance the authors suggest their
work solidifies the concept of chloride-sensitive hypertension.
It must be remembered that these studies don’t dispute that
Na is primary in maintaining blood volume and driving hypertension. However,
chloride absorption is a necessary requirement for the absorption of Na in the
setting of a salt load causing hypertension. Thus, Chloride might be the queen
and Na the king of extracellular solutes!
Na is primary in maintaining blood volume and driving hypertension. However,
chloride absorption is a necessary requirement for the absorption of Na in the
setting of a salt load causing hypertension. Thus, Chloride might be the queen
and Na the king of extracellular solutes!
Posted by Andrew Malone
