Why is hydrochlorothiazide an effective treatment for PHA 2. Familial hyperkalemic hypertension?
PHA 2 is a heterogeneous condition that can be transmitted in autosomal-dominant, autosomal-recessive, or de novo fashion. In addition to hypertension and hyperkalemia, patients feature hyperchloremic metabolic acidosis. Aldosterone levels are typically in the low normal range, reflecting the opposing effects of hyperkalemia, which normally stimulates aldosterone release, and extracellular fluid volume expansion, which normally inhibits it. Renin activity is typically suppressed. Hypercalciuria has been described.
The molecular mechanisms of PHA 2 is defined by activation of the sodium-chloride-cotransporter (NCCT) in the distal convoluted tubule (DCT). In addition to salt-sensitive hypertension, blood pressure is chloride dependent; the exchange of sodium bicarbonate or citrate infusions for sodium chloride infusion ameliorates blood pressure elevation. These findings explain why thiazide diuretics represent a highly effective treatment for all features of this syndrome.