Anatagonists to
angiotensin,
catecholamines,
aldosterone, and
vasopressin have long been used to help determine agonist roles in
hypertension. We here call attention to a possible extension of this approach to detect, evaluate, and treat vascular
sodium transport defects in
hypertension. Two basic types of transport defects have been identified in the blood vessels of hypertensive animals, increased
sodium permeability and decreased
sodium pump activity.
Intravenous injection of 6-iodo-amiloride, a
sodium channel blocker and
vasodilator, produces an immediate and sustained decrease in blood pressure in two genetic models of
hypertension characterized by increased permeability of the vascular smooth muscle cell membrane to
sodium (Okamoto spontaneously hypertensive rat, Dahl salt sensitive rat), whereas it produces only a transient fall in arterial pressure in two renal models of
hypertension having normal
sodium permeability in vascular smooth muscle cells (reduced renal mass-saline rat, one-kidney, one
clip rat).
Canrenone, a metabolic product of
spironolactone which can compete with oubain for binding to Na+,K+-
ATPase at the
digitalis receptor site, decreases blood pressure in a low
renin, volume expanded model of
hypertension which has been shown to have depressed
sodium pump activity in arteries and increased
sodium pump inhibitor in plasma (reduced renal mass-saline rat) but has no effect on blood pressure in a genetic model of
hypertension which has been shown to have increased
sodium pump activity secondary to increased
sodium permeability (spontaneously hypertensive rat). Thus, a
sodium channel blocker and a competitor to
ouabain binding can detect and determine the functional significance of
sodium transport defects in the blood vessels of intact hypertensive animals. Studies in red and white blood cells suggest that similar defects may exist in the blood vessels of hypertensive humans. Thus, this approach, probing for vascular transport defects in the intact animal, may ultimately also be useful in the clinical setting.