It appears, then, that sodium intake that exceeds 50 to 100 mmol per day is necessary but not sufficient for the
development of primary hypertension.
It is estimated an increase in blood pressure with age over a 30-year period (e.g., from 25 to 55 years of age); mean
systolic blood pressure was 5 mm Hg higher and diastolic blood pressure was 3 mm Hg higher when sodium intake
was increased by 50 mmol per day
Hypertension affects less than 1% of people in isolated societies but approximately one third of adults in
Potassium restriction causes a deficit in cellular potassium that triggers cells to gain sodium in order to maintain
their tonicity and volume.
Subsequent studies in rats showed that the pressor effect of potassium depletion requires abundant consumption of
sodium chloride (e.g., 4.5 g of sodium chloride per 100.0 g of dietary intake).
Potassium supplementation can reduce the need for antihypertensive medication.
Dietary potassium has been shown to exert a powerful, dose-dependent inhibitory effect on sodium sensitivity. An
increase in dietary potassium can even abolish sodium sensitivity in both normotensive and hypertensive subjects.
Human kidneys are poised to conserve sodium (viaAldosterone= retention->excress ECF and plasma volume but
NOT blood volume in primary htn) and excrete potassium. Prehistoric humans, who consumed a sodium-poor and
potassium-rich diet, were well served by this mechanism.
Ahigh sodium intake increases kaliuresis, especially when sodium reabsorption by the renal cortical collecting
tubule (where sodium reabsorption and potassium secretion are functionally linked) is enhanced (as it is in primary
hypertension). Skeletal muscle K decreases in untreated htn but serum K remains the same.
Na-H exchanger type 3- pivotal luminal transporter in proximal tubule and thick ascending limb of loop of Henle
(bulk of Na resorption). Activated by htn and K depletion (induces intracellular acidosis and stimulates the SNS
and renin-angiotensin system. Other transporters in distal and collecting tubules are activated by aldosterone
excess in primary htn.
Additional mechanisms of sodium retention in primary hypertension: congenital reduction in the number of
nephrons, diminished renal medullary blood flow, and subtle acquired renal injury due to ischemia or interstitial
Polygenic effect->activating polymorphisms in the genes encoding G protein–coupled receptor kinases (which
regulate dopamine receptors involved in sodium reabsorption in the renal proximal tubule) and α-adducin (a
cytoskeletal protein modulating the activity of the renal sodium pump).
Arterial Wall Sodium retention (via digitalis-like factor release by adrenal glands and the brain) and K deficit or hypokalemia ->
Inhibition of sodium pump increases calcium (via stimulation of sodium-calcium exchange type 1) in the cell and
decreases membrane potential (depolarization) in the vascular smooth muscle cells->
further rise in intracellular Ca++ (volt-rep channels, SR and Na-Ca exchanger)->
Vascular smooth muscle contraction
Note: PST 2238 (rostafuroxin) antagonizes effects of digitalis-like factor in the vascular and renal sodium pump
SEA0400 inhibits the Na-Ca exchanger type 1.