Amiloride-sensitive lithium reabsorption during doxazosin-induced blood pressure reduction in rats.
1. The effects of acute systemic alpha 1-adrenoceptor blockade by doxazosin on glomerular filtration rate, urine flow, sodium clearance and lithium clearance were investigated in acutely prepared conscious rats. 2. Clearance experiments were performed during water diuresis (20 mmol/l NaCl and 110 mmol/l glucose, 3 ml/h). After a control period, animals were randomized to one of the following treatments: time-control (n = 9), doxazosin (50 micrograms primer, 30 micrograms h-1 kg-1) (n = 10), amiloride (1 mg primer; 2.4 mg h-1 kg-1) (n = 10) and doxazosin plus amiloride (n = 9). 3. Doxazosin reduced the mean arterial blood pressure from 125 to 108 mmHg; this was associated with transient reductions in glomerular filtration rate, urine flow and lithium clearance. After the transient antidiuresis, the sodium excretion rate remained reduced in doxazosin-infused animals. Amiloride increased the sodium excretion rate without having effects on other variables. When doxazosin was given together with amiloride, the reduction in lithium clearance observed during the transient reduction in glomerular filtration rate and urine flow, was partly abolished. Thus the fractional lithium excretion was transiently increased in rats given doxazosin plus amiloride (from 29 to 40%), whereas in rats given doxazosin alone a non-significant reduction was observed (from 28 to 25%). The dissociation between lithium clearance and fractional lithium excretion in the two doxazosin-infused groups was only significant during the transient reduction in glomerular filtration rate and urine flow. 4. The results provide evidence for an amiloride-sensitive lithium reabsorption during acute systemic alpha 1-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Petersen
J S
JS
Department of Pharmacology, University of Copenhagen, Denmark.
Shalmi
M
M
Bak
M
M
Lomholt
N
N
Christensen
S
S
D000042:Absorption; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017292:Doxazosin; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008094:Lithium / Q000378:metabolism*; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D014554:Urination / Q000187:drug effects
D000959:Antihypertensive Agents; D000584:Amiloride; D008094:Lithium; D012964:Sodium; D017292:Doxazosin; D011224:Prazosin