ABNORMALITIES OF NASAL POTENTIAL DIFFERENCE MEASUREMENT IN LIDDLES-SYNDROME

In fiddle's syndrome, a rare inherited form of hypertension, epithelia l sodium channel mutations appear to cause high blood pressure by incr easing sodium reabsorption through sodium channels in the renal distal tubule. This increase in channel activity has not been confirmed prev iously by in vivo measurement, We have made transnasal potential diffe rence measurements (effective in detection of increased sodium channel activity in cystic fibrosis) in three brothers with genetically prove n fiddle's syndrome, their unaffected sister, and 40 normotensive cont rols. Maximum potential difference after 2 wk off treatment in the aff ected brothers was -30.4+/-1.2 mV (values mean+/-SD, lumen-negative wi th respect to submucosa) and was significantly more lumen-negative tha n that of the control group (-18.6+/-6.8 mV, P = 0.0228) or the unaffe cted sister (-18.25 mV, P < 0.01), The change in potential difference after topical application of 10(-4) M amiloride was greater in the fid dle's patients, 14.0+/-2.1 mV, than in controls (7.9+/-3.9 mV, P = 0.0 126) or the unaffected sister (5.5 mV, P < 0.05), This is the first in vivo demonstration of increased sodium channel activity in fiddle's s yndrome, If these results are confirmed in other kindreds with this co ndition, then nasal potential difference measurements could provide a simple clinical test for fiddle's syndrome.