Effects of naftidrofuryl on isolated perfused kidneys of spontaneously hypertensive rats.
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) F1 alpha and thromboxane (Tx)B2, the stable end-products of PGI2 and TxA2, respectively. 3. NA increased renal vascular resistance and GFR in a dose-dependent manner and enhanced the venous excretion of 6-keto-PGF1 alpha and TxB2. 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-PGF1 alpha excretion. 4. 5-HT increased renal vascular resistance but not GFR. It did not change the sodium excretion and the release of 6-keto-PGF1 alpha and TxB2. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
B L
BL
Department of Physiology and Clinical Pharmacology, Faculty of Pharmacy, Lyon, France.
Liu
K L
KL
Sacquet
J
J
Wiernsperger
N
N
Benzoni
D
D
Sassard
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009257:Nafronyl / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012701:Serotonin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D012701:Serotonin; D009257:Nafronyl; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D009638:Norepinephrine