The Effects of Physostigmine, L-Arginine and NG-Nitro-L-Arginine Methyl Ester (L-NAME) on the Mean Arterial Pressure of the Rat

Abstract

The effects of physostigmine, L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) were investigated in urethane-anaesthetized rats. The drugs were chosen because physostigmine has been known to produce an increase in peripheral adrenergic activity, whereas L-arginine and L-NAME have been known to modulate nitric oxide (NO) production. Slow infusion of L-arginine produced significant hypotension, but only in animals pretreated by physostigmine. L-NAME applied in the same way produced a slow developing increase in blood pressure, but not in animals pretreated by physostigmine. The pressor responses to physostigmine were potentiated if the drug was injected during infusion of L-NAME, and depressed if the drug was injected after stopping L-NAME infusion (in rats not pretreated with physostigmine). It is concluded that L-arginine-NO pathways act in vivo to oppose peripheral vasoconstrictor influences coupled with central cholinergically mediated activation of the adrenergic system, as produced by physostigmine. In this way, NO is part of a general mechanism for blood pressure regulation.

L-arginine and physostigmine in hemorrhagic shock: Lack of evidence for synergism

“…Physostigmine-induced a raise of the mean arterial pressure (MAP) in rabbits subjected to severe hypovolemia (approx. 40% of the estimated blood volume for 15 min) ( Table 1) could be explained by several mechanisms Savi} et al, 1991Savi} et al, , 1992@uni} et al, 1995;Prostran et al, 1994Prostran et al, , 1996Prostran et al, , 1997. First, its central cholinergically-mediated stimulation of the peripheral sympathetic tonus and the release of vasopressin could contribute to defence mechanisms in shock.…”

“…Physostigmine has been extensively used in various models of hemorrhagic shock with remarkable success (Guarini et al, 1989;Savi} et al, 1991Savi} et al, , 1992@uni} et al, 1995;Todorovi} et al, 1996Todorovi} et al, , 1997. As a lipid-soluble anticholinestrase, it is distributed in the central nervous system and may increase blood pressure via central cholinergically mediated activation of the peripheral adrenergic system (Varagi}, 1955;Prostran et al, 1994Prostran et al, , 1996Prostran et al, , 1997. However, the beneficial effects of physostigmine (0.07 mg/kg, i.v.…”

“…The interaction between L-arginine and physostigmine was extensively investigated in normotensive and spontaneously hypertensive non-hemorrhaged rats (Prostran et al, 1994(Prostran et al, , 1997. Such investigations may be of a great importance in the elucidation of the role of peripheral and central mechanisms of beneficial actions of both physostigmine and L-arginine in hemorrhagic shock.…”

The importance of potassium channels in the mechanism of the relaxing effect of pentoxifylline on isolated rat uteri

“…Running title: Potassium Channels in the Mechanism of Action of Pentoxifylline sive rats, but only in animals pretreated with physostigmine. 14 Experiments on animals have shown the presence of increased NO synthesis during normal pregnancy. In humans, a lack of NO causes vasoconstriction and preeclampsia.…”