Sodium space and intravascular volume: dietary sodium effects in cystic fibrosis and healthy adolescent subjects.

OBJECTIVE: To assess the physiologic response to salt depletion in subjects with cystic fibrosis (CF) and control male adolescents for sodium balance, sodium space, and stimulation of the renin-angiotensin-aldosterone axis. DESIGN: Seven subjects with CF and six controls received a salt-replete (150 or 290 mmol NaCl per day) diet and then a salt-deplete (10 mmol NaCl per day) diet while in a clinical research center. RESULTS: Space maintenance: CF subjects responded to salt depletion with a greater weight loss than did controls (1.9 vs 0.8 kg) and a decrease in 24Na+ space, whereas controls maintained 24Na+ space. Paired (Na-deplete/Na-replete) blood volumes decreased in subjects with CF, but not in controls. Renin-angiotensin-aldosterone axis stimulation: During salt repletion, subjects with CF had significantly higher aldosterone values than did controls in the afternoon, but not at 7:00 AM. During salt depletion, plasma renin activity and aldosterone increased significantly more in subjects with CF than in controls (renin, 35 vs 13 ng/mL/hour [9.7 vs 3.6 ng.L-1 s-1]; aldosterone: 181 vs 101 ng/dL [5021 vs 2802 pmol/L]). Furthermore, the angiotensin antagonist saralasin increased renin much more in subjects with CF (154 vs 36 ng/mL per hour [43 vs 10 ng.L-1 s-1]). Vasomotor functions: Mean arterial pressure was decreased in subjects with CF on both diets and decreased significantly more with low salt only in subjects with CF. During salt depletion, subjects with CF showed enhanced orthostatic tolerance (less heart rate increase with standing) compared with controls, thus obscuring their volume loss. The blood pressure response to an acute infusion of saralasin suggested that in salt-replete subjects with CF, but not in controls, angiotensin receptors were functional in maintaining vascular tone. During salt depletion, angiotensin was more important for maintenance of blood pressure in subjects with CF than in controls, because the saralasin-induced drop in blood pressure was 20%, ie, close to shock levels, in subjects with CF, and only 6% in controls. CONCLUSION: The data suggest that patients with CF are so successful in compensating for volume depletion by vigorous activation of the renin-angiotensin system that salt depletion/dehydration cannot be recognized easily by routine clinical measurements, eg, capillary refill, serum sodium levels, or tachycardia.

Inhibition of amiloride-sensitive sodium conductance by indoleamines.

To examine a possible role of indoleamines in the regulation of epithelial sodium absorption, the effect of serotonin (5-hydroxytryptamine) and several derivatives on electrolyte transport was measured in vitro in the baboon bronchus and in the trachea and colon of sodium-deficient rats. Serotonin, melatonin (N-acetyl-5-hydroxytryptamine), and harmaline (1-methyl-7-methoxy-3,4-dihydro-beta-carboline) inhibited sodium transport in all three preparations in a similar manner to the natriuretic agent amiloride. In all three epithelia, sodium absorption via the amiloride-sensitive pathway constitutes a substantial portion of total electrolyte transport, measured as the amiloride-sensitive short-circuit current. Thus 25 microM amiloride inhibited the short-circuit current 21% in the rat trachea, 63% in the baboon bronchus, and 90% in the rat colon. Serotonin, melatonin, and harmaline inhibited the amiloride-sensitive portion of the short-circuit current from the luminal side of the epithelium. The inhibition was rapid, requiring only seconds, and maximal inhibition by serotonin was identical to that by amiloride. When sodium was omitted from the luminal solution, the short-circuit current was reduced a similar amount, suggesting that sodium absorption was being inhibited by both amiloride and the indoles. The IC50 value for amiloride was 50 nM in the baboon bronchus and 500 nM in the rat colon. In contrast, the IC50 value for serotonin was 0.4 mM in the baboon bronchus and 8 mM in the rat colon. These results, together with the wide distribution of amine-precursor-uptake-and-decarboxylation (APUD) cells in the respiratory and intestinal tract, suggest that certain indoleamines could play a role as local regulators of fluid and electrolyte transport. For example, in the airways, indoleamines may be one of the factors involved in regulation of the depth of the periciliary fluid layer.