Alpha-1 blockade inhibits compensatory sodium reabsorption in the proximal tubules during furosemide-induced volume contraction.
The renal effects of alpha-1 adrenoceptor blockade (i.v. infusion of doxazosin, 50 micrograms/kg prime; 30 micrograms/kg/h) on tubular sodium reabsorption during acute furosemide-induced volume contraction (i.v. infusion of furosemide, 7.5 mg/kg/h for 3 h) was investigated by clearance technique in conscious rats. By measuring inulin clearance, lithium clearance and urinary excretion rates of sodium and water, the changes in proximal and distal tubular sodium handling were dissociated. In furosemide-infused rats given doxazosin (n = 11) or volume replacement (n = 9), the fractional lithium excretion increased from 30% (control) to a steady-state value of 51% (last hour of furosemide infusion), whereas in rats infused with furosemide only (n = 9), the fractional lithium excretion increased transiently to a peak value of 52% and then declined to a steady-state value of 39%. Doxazosin attenuated the acute natriuretic response to furosemide by 54%, mainly due to increased sodium reabsorption in the distal nephron segment. This effect was associated with a significant lower mean arterial pressure compared with rats given furosemide only. The results are compatible with a contributory role of proximal tubular alpha-1 adrenoceptors in mediating compensatory Na reabsorption during furosemide-induced volume contraction.
Department of Pharmacology, University of Copenhagen, Denmark.
J S
JS
Petersen
M
M
Shalmi
U
U
Abildgaard
S
S
Christensen
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D017292:Doxazosin; D004347:Drug Interactions; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000378:metabolism; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D005665:Furosemide; D008094:Lithium; D012964:Sodium; D017292:Doxazosin; D011224:Prazosin