Spontaneous nitric oxide release accounts for the potent pharmacological actions of FK409
| Autor: | Yasuhiro Kita, Mie Nishio, Kazuhiro Maeda, Keizo Yoshida, Yoshimi Hirasawa |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Contraction (grammar) Platelet Aggregation Stereochemistry Muscle Relaxation Vasodilator Agents Administration Oral Blood Pressure Urine In Vitro Techniques Pharmacology Nitric Oxide Muscle Smooth Vascular Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Drug Stability Nitrate medicine Animals Humans Cyclic GMP Aorta Biological activity Hydrogen-Ion Concentration Nitro Compounds In vitro Rats Adenosine Diphosphate chemistry Mechanism of action Isosorbide dinitrate medicine.symptom Platelet Aggregation Inhibitors Muscle Contraction medicine.drug |
| Zdroj: | European Journal of Pharmacology. 257:123-130 |
| ISSN: | 0014-2999 |
| Popis: | (±)-( E )-Ethyl-2-[( E )-hydroxyimino]-5-nitro-3-hexeneamide (FK409), which was isolated from microbial products, has been reported to show a vasorelaxant effect through a mechanism similar to that of the organic nitrates such as isosorbide dinitrate. In solution at pH 7.4, FK409 decomposed and released nitric oxide (NO) spontaneously, while isosorbide dinitrate did not. In in vitro biological tests, FK409 inhibited norepinephrine-induced contraction in rat isolated aorta more potently than did isosorbide dinitrate (ED 50 = 1.0 and 310 nM, respectively) and ADP-induced human platelet aggregation (IC 50 = 0.75 and > 100 μ M, respectively). Nitrate/nitrate was recovered in urine accumulated for 24 h after collection from rats given FK409 or isosorbide dinitrate (10 mg/kg p.o.). FK409 (10 mg/kg p.o.) increased the plasma cyclic GMP level and at the same time decreased the mean blood pressure in conscious rats, while isosorbide dinitrate (10 mg/kg p.o.) did not change these parameters significantly. These results suggest that FK409 produces these pharmacological actions via spontaneously released NO, unlike isosorbide dinitrate, and has possibility of becoming a unique orally drug for cardiovascular diseases as a new NO donor. |
| Databáze: | OpenAIRE |
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