Antiproliferative and endothelium-dependent vasodilator properties of 1,3-dihydro-3-p-chlorophenyl-7-hydroxy-6-methyl-furo-(3,4c) pyridine hydrochloride (cicletanine).
The vasodilator and antiproliferative actions of 1,3-dihydro-3-p-chlorophenyl-7-hydroxy-6-methyl-furo-(3,4c) pyridine hydrochloride (cicletanine) were studied on mesenteric resistance arteries and cultured mesenteric artery myocytes of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Cicletanine (20-200 microM) induced relaxation of endothelium-intact mesenteric resistance arteries of SHR and WKY precontracted with norepinephrine. No difference in sensitivity was observed (SHR IC50 = 77 +/- 12 microM vs. 83.3 +/- 7.4 microM for WKY, N.S.). Endothelial denudation of WKY vessels significantly attenuated the relaxing action of cicletanine (IC50 + endo = 83 +/- 7.4 microM vs. IC50 - endo = 135 +/- 9.7 microM; P < .001) and had a similar, but nonsignificant effect on SHR (IC50 + endo = 77 +/- 12 microM vs. IC50 - endo = 117 +/- 14.5 microM; P = .065). Preincubation of endothelium-intact vessels with nitro-L-arginine methyl ester significantly attenuated cicletanine-induced relaxation in WKY, but not SHR vessels; 0.1 mM Ba++ had a similar effect. Preincubation with 3 microM indomethacin was without effect on relaxation of vessels of either strain. Cicletanine (100-1000 microM) inhibited proliferation of cultured superior mesenteric artery muscle cells growing in the presence of either 10% (SHR IC50 = 440 +/- 24 microM vs. 517 +/- 12 microM for WKY; P < .05) or 2% fetal bovine serum. This antiproliferative action was fully reversible, partially inhibited by indomethacin in SHR myocytes and was associated with a decrease in [3H]thymidine uptake in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Bukoski
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RD
Department of Internal Medicine, University of Texas Medical Branch, Galveston.
Bo
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D011725:Pyridines; D014665:Vasodilator Agents; C038068:cicletanine