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Effects of the calcium channel blocker AE0047 on renal function in conscious spontaneously hypertensive rats: Focus on renal proximal tubules
Author(s) -
Hayashi Kazutaka,
Kido Hideaki,
Kubo Yoshiji,
Shinyama Hiroshi,
Nakamura Norifumi,
Kagitani Yoshio
Publication year - 1997
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199706)41:2<91::aid-ddr6>3.0.co;2-m
Subject(s) - natriuresis , diuretic , diuresis , endocrinology , medicine , reabsorption , uric acid , renal function , renal sodium reabsorption , chemistry , kidney , excretion , calcium channel blocker , pharmacology , blood pressure
The hypotension induced by peripheral vasodilators is occasionally accompanied by diminished urine formation induced via various anti‐diuretic mechanisms. The question of whether an antihypertensive agent has diuretic action is therefore relevant to its usefulness. In the present study, conducted in conscious, spontaneously hypertensive rats (SHR), the lithium clearance technique was used to investigate the effect of intravenously administered AE0047 on renal function; the effect of orally administered AE0047 on uric acid excretion was also investigated. Intravenous injection of AE0047 (10 and 30 μg/kg) produced potent hypotension, accompanied by diuresis and natriuresis. The diuretic action was accompanied by an elevation of FE Na and FE Li levels, with minimal change in GFR. Oral administration of AE0047 (1 and 3 mg/kg) led to a dose‐related increase in urine volume and in urinary excretion of sodium and uric acid (U UA V). Simultaneous administration of pyrazinamide, an inhibitor of uric acid secretion in proximal tubules, mitigated the increase in U UA V. These findings indicate that systemically administered AE0047 produces diuresis and natriuresis, in part via an inhibition of sodium and water reabsorption in the proximal tubules. The action of AE0047 at renal proximal tubular sites thus offers benefit in hypertension therapy. Drug Dev. Res. 41:91–98, 1997. © 1997 Wiley‐Liss, Inc.