SELECTIVE ALPHA-1-ADRENOCEPTOR BLOCKADE AND RENAL SODIUM HANDLING IN HUMANS

In animal studies, acute interruption of the activity of renal alpha-1 adrenoceptors by renal denervation results in an increase in sodium and water excretion. Chronic selective blockade of alpha-1 adrenoceptors by prazosin in clinical practice has been associated with sodium retention, however. Previous studies in the authors' laboratory using chronic alpha-1 blockade in the rat have demonstrated a decreased ability to excrete a saline load. Therefore, the authors determined the effect of chronic selective alpha-1 adrenoceptor blockade with prazosin in eight healthy volunteers. Volunteers underwent a water load to establish a water diuresis, followed by a modest saline load using intravenous saline (0.9% NaCl). This experimental protocol was repeated after four weeks of prazosin therapy (5 mg twice daily). Prazosin failed to alter body weight (73.6 +/- 4.2 versus 74.5 +/- 4.1 kg, expressed as mean +/- standard error), mean blood pressure (86.7 +/- 2.7 versus 84.7 +/- 2.3 mm Hg), creatinine clearance (127.0 +/- 8.5 versus 133.4 +/- 12.0 mL/min), renal blood flow as measured by para-aminohippurate clearance (1202 +/- 88 versus 1175 +/- 69 mL/min) and the 24-hour sodium excretion (115 +/- 11 versus 128 +/- 19 mmol). In the presence of the experimentally induced saline load, chronic prazosin treatment was associated with a decreased free water clearance (e.g., hour 3, 7.8 +/- .7 versus 6.3 +/- 2.0 mL/min; P less-than-or-equal-to .05) and fractional excretion of sodium (e.g., hour 3, 1.48 +/- .10 versus 1.15 +/- .13; P less-than-or-equal-to .05). The cumulative sodium excretion of the four 1-hour urine collection periods during and after the saline infusion was decreased after the prazosin treatment (79.4 +/- 7.8 versus 64.1 +/- 6.1 mmol/4 hours; P less-than-or-equal-to .05). These results demonstrate that in normal volunteers, selective alpha-1 adrenoceptor blockade with prazosin decreases the ability to excrete a modest saline load. These observations may explain, in part, the sodium retention observed clinically with chronic prazosin treatment.