L-NAME in the cardiovascular system - nitric oxide synthase activator?
L-arginine analogues are widely used inhibitors of nitric oxide synthase (NOS) activity both in vitro and in vivo, with N(ω)-nitro-L-arginine methyl ester (L-NAME) being at the head. On the one hand, acute and chronic L-NAME treatment leads to changes in blood pressure and vascular reactivity due to decreased nitric oxide (NO) bioavailability. However, lower doses of L-NAME may also activate NO production via feedback regulatory mechanisms if administered for longer time. Such L-NAME-induced activation has been observed in both NOS expression and activity and revealed considerable differences in regulatory mechanisms of NO production between particular tissues depending on the amount of L-NAME. Moreover, feedback activation of NO production by L-NAME seems to be regulated diversely under conditions of hypertension. This review summarizes the mechanisms of NOS regulation in order to better understand the apparent discrepancies found in the current literature.
Department of Physiology, Jessenius Faculty of Medicine, Comenius University, Malá Hora 4A, 036 01 Martin, Slovak Republic. jana.kopincova@jfmed.uniba.sk
Jana
J
Kopincová
Angelika
A
Púzserová
Iveta
I
Bernátová
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester