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 < or = .05) and fractional excretion of sodium (e.g., hour 3, 1.48 +/- .10 versus 1.15 +/- .13; P < or = .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Penner
S B
SB
Department of Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Stanko
C K
CK
Smyth
D D
DD
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004231:Diuresis; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D011224:Prazosin / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine*; D012965:Sodium Chloride / Q000008:administration & dosage
D011942:Receptors, Adrenergic, alpha; D012965:Sodium Chloride; D012964:Sodium; D011224:Prazosin