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EFFECTS OF NAFTIDROFURYL ON ISOLATED PERFUSED KIDNEYS OF SPONTANEOUSLY HYPERTENSIVE RATS
Author(s) -
Zhang B. L.,
Liu K. L.,
Sacquet J.,
Wiernsperger N.,
Benzoni D.,
Sassard J.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01648.x
Subject(s) - endocrinology , medicine , prostanoid , excretion , vascular resistance , thromboxane , chemistry , renal function , prostaglandin , spontaneously hypertensive rat , renal blood flow , blood pressure , platelet
SUMMARY 1. Experiments were designed to determine the effects of low concentrations (5–500 nmol/L) of naftidrofuryl, a 5‐hydroxytryptamine (5‐HT) antagonist, on renal functions and prostanoid synthesis responses to noradrenaline (NA) and 5‐HT. Isolated kidneys of 8 week old male spontaneously hypertensive rats were perfused at a constant flow rate in a single‐pass system. 2. In baseline conditions, naftidrofuryl did not modify the renal vascular resistance and the glomerular filtration rate (GFR), although it elicited a significant but not dose‐dependent increase in the venous excretion of 6‐keto‐prostaglandin (PG) F 1α and thromboxane (Tx)B 2 , the stable end‐products of PGI 2 and TxA 2 , respectively. 3. NA increased renal vascular resistance and GFR in a dose‐dependent manner and enhanced the venous excretion of 6‐keto‐PGF 1α and TxB 2 . Naftidrofuryl significantly attenuated the effects of NA on renal vascular resistance, abolished those on GFR and enhanced, at the highest concentration (500 nmol/L) only, those on 6‐keto‐PGF 1α excretion. 4. 5‐HT increased renal vascular resistance but not GFR. It did not change the sodium excretion and the release of 6‐keto‐PGF 1α and TxB 2 . Naftidrofuryl blunted the RVR response to 5‐HT without change in the prostanoid release. The inhibitory action of naftidrofuryl was not modified by indomethacin which, by itself, prevented the vasoconstrictor response to 5‐HT. 5. It is concluded that, in isolated perfused kidneys of SHR, naftidrofuryl inhibits the contractile response to 5‐HT and NA; this effect is not dependent upon changes in synthesis of PGI 2 or TxA 2 and the vasoconstrictor effect of 5‐HT involves the release of a cyclooxygenase metabolite that differs from TXA 2 .