Selective Alpha‐1 Adrenoceptor Blockade and Renal Sodium Handling in Humans

Publisher Website
Google Scholar
Abstract
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 ≤ .05) and fractional excretion of sodium (e.g., hour 3, 1.48 ± .10 versus 1.15 ± .13; P ≤ .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 ≤ .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.