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 a nd water excretion. Chronic selective blockade of alpha-1 adrenoceptor s by prazosin in clinical practice has been associated with sodium ret ention, however. Previous studies in the authors' laboratory using chr onic alpha-1 blockade in the rat have demonstrated a decreased ability to excrete a saline load. Therefore, the authors determined the effec t of chronic selective alpha-1 adrenoceptor blockade with prazosin in eight healthy volunteers. Volunteers underwent a water load to establi sh a water diuresis, followed by a modest saline load using intravenou s saline (0.9% NaCl). This experimental protocol was repeated after fo ur weeks of prazosin therapy (5 mg twice daily). Prazosin failed to al ter body weight (73.6 +/- 4.2 versus 74.5 +/- 4.1 kg, expressed as mea n +/- 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 cleara nce (1202 +/- 88 versus 1175 +/- 69 mL/min) and the 24-hour sodium exc retion (115 +/- 11 versus 128 +/- 19 mmol). In the presence of the exp erimentally induced saline load, chronic prazosin treatment was associ ated with a decreased free water clearance (e.g., hour 3, 7.8 +/- .7 v ersus 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 fo ur 1-hour urine collection periods during and after the saline infusio n 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 dem onstrate that in normal volunteers, selective alpha-1 adrenoceptor blo ckade with prazosin decreases the ability to excrete a modest saline l oad. These observations may explain, in part, the sodium retention obs erved clinically with chronic prazosin treatment.