RT Journal Article
SR Electronic
T1 Effects of Renal Papillary-Medullary Lesion on the Antihypertensive Effect of Furosemide and Development of Salt-Sensitive Hypertension in Dahl-S Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1415
OP 1422
VO 280
IS 3
A1 Ketil Haugan
A1 Michael Shalmi
A1 Jørgen Søberg Petersen
A1 Niels Marcussen
A1 Jesper Spannow
A1 Sten Christensen
YR 1997
UL http://jpet.aspetjournals.org/content/280/3/1415.abstract
AB 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 NaCl-sensitive hypertension in rats with BEA-induced renal papillary-medullary lesion is related to an impaired ability to excrete excess NaCl. The American Society for Pharmacology and Experimental Therapeutics