Vasorelaxant activity of some oxime derivatives.
Several non-aromatic substituted oxime derivatives (formamidoxime, acetaldoxime, acetone oxime, acetohydroxamic acid, formaldoxime) function as vasorelaxant NO donors when added to precontracted aortic rings in vitro. This study was aimed to evaluate whether these substances posses vasodilator properties under in vivo conditions. We studied blood pressure changes elicited by administration of these compounds to conscious chronically catheterized Wistar rats in which endogenous NO synthesis was acutely inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME) pretreatment (30 mg/kg i.v.). Three of the tested substances (formaldoxime, acetohydroxamic acid and formamidoxime) induced pronounced dose-dependent blood pressure reduction which was further augmented when baroreflex operation was interrupted by ganglionic blockade (5 mg/kg pentolinium). Pretreatment of rats with methylene blue (soluble guanylate cyclase inhibitor) was used to estimate the contribution of NO to observed blood pressure lowering effects of the above compounds. Nitric oxide seems to be responsible for the entire formaldoxime-induced blood pressure decrease and for a considerable part of blood pressure changes elicited by formamidoxime. On the contrary, we did not find a significant NO contribution to blood pressure reduction caused by acetohydroxamic acid. In conclusion, our study confirmed in vivo vasodilator effects of three above mentioned compounds which were earlier demonstrated to induce in vitro vasorelaxation. It indicated a variable contribution of nitric oxide to blood pressure changes elicited by particular compounds. Substances with hydrophilic character (formamidoxime, acetohydroxamic acid, formaldoxime) were effective, whereas less hydrophilic substance (acetaldoxime) or slightly hydrophobic one (acetone oxime) were ineffective.
Jaros
Filip
F
Chair of Biochemistry, Faculty of Sciences, Charles University, Czech Republic.
Straka
Tomás
T
Dobesová
Zdenka
Z
Pintérová
Mária
M
Chalupský
Karel
K
Kunes
Jaroslav
J
Entlicher
Gustav
G
Zicha
Josef
J
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010091:Oximes / Q000494:pharmacology*; D010425:Pentolinium Tartrate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D010091:Oximes; D014665:Vasodilator Agents; D009569:Nitric Oxide; C484470:formaldoxime; C006358:acetohydroxamic acid; D010425:Pentolinium Tartrate; C023728:acetaldehyde oxime; D019331:NG-Nitroarginine Methyl Ester