Effect of ACE inhibitors on atrial natriuretic factor in the brains of rats with reduced renal mass.
We tested the effect of renal insufficiency, with and without angiotensin (Ang) converting enzyme (ACE) inhibition, on blood and brain atrial natriuretic factor (ANF) in rats. Two ACEs, one which penetrates into the CNS and one which does not, were used to distinguish between peripheral and central ACE effects. Rats underwent 5/6 nephrectomy (5/6-NPX) by ligation of renal arterial branches. After seven days, 28 5/6-NPX rats received lisinopril 20 mg/kg/day and 28 5/6-NPX rats received quinapril 30 mg/kg/day orally for five days, while 28 5/6-NPX control rats and 28 sham rats did not. Body weight, blood pressure, drinking and urine volume were monitored. At sacrifice, urine, plasma, and brain tissue was collected. ANF in 16 brain areas was measured by radioimmunoassay. 5/6-NPX resulted in increased blood pressure, increased urine volume, proteinuria, and increased drinking. Both ACEs lowered blood pressure to sham values and decreased proteinuria. Both ACEs increased plasma renin activity and decreased plasma ANF. However, only lisinopril decreased drinking and urine volume. 5/6-NPX increased ANF values in six brain areas, namely the periventricular preoptic nucleus, the arcuate nucleus, the perifornical nucleus, the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus compared to sham rats. These same increases in brain ANF were also observed in 5/6-NPX rats given quinapril, compared to shams. However, lisinopril lowered ANF to sham levels in the periventricular preoptic nucleus, the arcuate nucleus, and the perifornical nucleus. In the three additional brain areas, namely the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus, lisinopril did not effect the elevated ANF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine-Nephrology, University of Erlangen-Nürnberg, Germany.
H
H
Geiger
U
U
Bahner
I
I
Kraus
M
M
Hoffmann
M
M
Palkovits
A
A
Heidland
F C
FC
Luft
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D004326:Drinking / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D017706:Lisinopril; D008297:Male; D009392:Nephrectomy; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000378:metabolism* / Q000503:physiopathology; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D009320:Atrial Natriuretic Factor; D017706:Lisinopril; D000077583:Quinapril