Effects of renal papillary-medullary lesion on the antihypertensive effect of furosemide and development of salt-sensitive hypertension in Dahl-S rats.
To test the hypothesis that the long-term antihypertensive action of furosemide is mediated by a renomedullary vasodepressor substance, we measured mean arterial pressure (MAP) by radiotelemetry in Dahl-S rats with either intact or bromoethylamine-induced (BEA, 100 mg/kg i.p.) lesion of the renal papilla and medulla. Seven days of recovery after BEA administration, the rats diet was changed from 1 to 4% NaCl, and during days 8 to 31, rats were randomized to daily treatment with placebo or furosemide (50 mg/kg p.o.). Then furosemide treatment was stopped and the rat food was changed to 1% NaCl diet. After a 10-day wash-out period, renal function was measured. BEA produced a rapid (within min) and sustained increase in MAP which was accelerated during 4% NaCl diet. Furosemide prevented 4% NaCl-induced hypertension in both rats with intact kidneys and in rats with BEA-induced renal papillary-medullary lesion. A significant decrease in renal plasma flow (-34%) and glomerular filtration rate (-40%) was observed in all BEA-treated rats independent of previous furosemide treatment. In response to an i.v. load of isotonic saline (10% body weight), rats with renal papillary-medullary lesion had an impaired ability to excrete sodium. Histological examination showed that BEA-treated rats had severe lesions of the renal papilla and medulla, with light-to-moderate changes in the renal cortex. It is concluded that the antihypertensive effect of furosemide is not mediated by a renomedullary vasodepressor substance. The accelerated NaCI-sensitive hypertension in rats with BEA-induced renal papillary-medullary lesion is related to an impaired ability to excrete excess NaCl.
Haugan
K
K
Department of Pharmacology, University of Copenhagen, Denmark.
Shalmi
M
M
Petersen
J S
JS
Marcussen
N
N
Spannow
J
J
Christensen
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001835:Body Weight; D004195:Disease Models, Animal; D004327:Drinking Behavior; D005665:Furosemide / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride
D000959:Antihypertensive Agents; D012965:Sodium Chloride; D005665:Furosemide