Modification of pressure natriuresis by long-term losartan in spontaneously hypertensive rats.
The goal of this study was to determine how long-term treatment of spontaneously hypertensive rats with losartan affects the pressure-natriuresis curve. Rats were treated with losartan (12 to 15 mg.kg-1.d-1 in drinking water) starting at 4 to 5 weeks of age. At 8 to 9 weeks of age, pressure natriuresis was studied in treated and untreated anesthetized rats using a preparation involving volume expansion and fixed neural and hormonal influences on the kidney. In some untreated rats, losartan (10 or 30 mg.kg-1 i.v.) was given acutely. Average initial mean arterial pressure (+/- SEM) for untreated rats was 164 +/- 2 mm Hg (n = 13) and 131 +/- 3 mm Hg (n = 13) for rats treated chronically with losartan (P < .01). Short-term losartan did not alter arterial pressure significantly. Glomerular filtration rate was not altered significantly by losartan, and renal blood flow was increased modestly by long- and short-term (10 mg.kg-1) losartan at several levels of renal artery pressure. At renal artery pressures of 130 to 175 mm Hg, there were no significant differences between untreated and short-term losartan rats for urine flow, total and fractional sodium excretions, and renal interstitial hydrostatic pressure. The relation between renal artery pressure and urine flow, sodium excretion, or fractional sodium excretion was shifted to the left by long-term losartan treatment. At identical renal artery pressures, renal interstitial hydrostatic pressure was not significantly different among losartan-treated (short or long term) and respective control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Kline
R L
RL
Department of Physiology, University of Western Ontario, London, Canada.
Liu
F
F
D000284:Administration, Oral; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D019808:Losartan; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan