Chronic administration of furosemide augments renal weight and glomerular capillary pressure in normal rats.
Angiotensin II (ANG II) is believed to promote progressive renal injury via augmented glomerular capillary hydraulic pressure (PGC). Acute volume reduction secondary to diuretic administration increases circulating ANG II and augments PGC, yet the hemodynamic effects of sustained diuretic administration are unknown. Therefore, glomerular micropuncture studies were performed in male Munich-Wistar rats after 6-8 wk of treatment with daily furosemide (F, 40 mg/day), furosemide plus the AT1 receptor antagonist, losartan (F + L, 5 mg/day), or no therapy (C, control). Renal weight was increased in F rats (1.23 +/- 0.7 g) vs. C (1.00 +/- 0.06 g) or F + L (0.97 +/- 0.01 g). In addition, PGC was elevated in F animals (52.1 +/- 1.5 mmHg) vs. C (43.7 +/- 1.5) or F + L-treated rats (41.3 +/- 1.7). F-treated rats were also characterized by a relative increase in efferent arteriolar resistance and filtration fraction. The latter was markedly attenuated in F + L-treated animals. Collectively, these findings are consistent with an ANG II-mediated alteration in intrarenal hemodynamics. In contrast to acute volume manipulations, however, chronic furosemide augmented renal growth, whereas losartan administration completely arrested this phenomenon. Further studies are warranted to determine whether the hemodynamic and growth adaptations elicited by chronic F administration induce or accelerate renal injury.
Department of Pediatrics, Cardinal Glennon Children's Hospital and Saint Louis University Health Sciences Center, St. Louis, Missouri 63104, USA.
P H
PH
Lane
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LD
Tyler
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PG
Schmitz
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D057911:Angiotensin Receptor Antagonists; D005665:Furosemide; D019808:Losartan