In vivo effect of naftidrofuryl on 5-hydroxytryptamine-mediated constriction in rat peripheral microcirculation.
Naftidrofuryl is commonly used in treatment of peripheral vascular disease. Its vasodilator action has been partly explained by its inhibitory effect of 5-HT2 receptors on peripheral arteries in vitro. The purpose of this study was to test in vivo whether naftidrofuryl selectively inhibits 5-hydroxytryptamine (5-HT)-mediated constriction of large arterioles in the peripheral microcirculation. This constriction appears to be 5-HT2 receptor-mediated. Three separate protocols were used to test the effects of naftidrofuryl: chronic injection (15 mg/kg, i.p., twice daily for 5-6 days; n = 7), acute intravenous (i.v.) infusion (15 mg/kg over 30 min; n = 7), or topical application (5 x 10(-8) M, n = 6; 5 x 10(-7) M, n = 5; 5 x 10(-6) M, n = 5; 10(-5) M, n = 7). Male Sprague-Dawley rats (145-185 g body weight) were anesthetized with sodium pentobarbital (50 mg/kg) and the cremaster muscle was prepared for intravital video microscopy. Diameter response of arterioles (70-120 microns) to increasing concentrations of locally applied 5-HT (10(-8)-10(-4) M) was assessed. In rats receiving no drug treatment, 5-HT caused vasoconstriction of arterioles beginning at 10(-6) M and reaching approximately 40% constriction at 10(-4) M. These vasoactive responses were not altered by chronic daily doses or an acute infusion of naftidrofuryl. 5-HT responses obtained with and without naftidrofuryl applied directly into the cremaster-bath also had little effect on the arteriole response at each of the four concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Biophysics, University of Louisville, KY 40292.
L G
LG
Koch
N L
NL
Alsip
B D
BD
Feige
W B
WB
Wead
P D
PD
Harris
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009132:Muscles / Q000098:blood supply; D009257:Nafronyl / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D011985:Receptors, Serotonin; D012701:Serotonin; D009257:Nafronyl; D007650:Ketanserin