The effects of hypochlorite-induced oxidative stress on presynaptic M2-receptors at sympathetic nerve endings in the rat tail artery.
1 It was shown recently that stimulation of cardiac muscarinic M2-receptors revealed an enhanced negative inotropic response in isolated rat left atria after exposure to hypochlorite-induced oxidative stress. This phenomenon was not observed after stimulation of the cardiac A1-receptor, which like the M2-receptor is coupled to Gi-proteins. Since even the contractile response to M3-receptor stimulation was not amplified in the rat portal vein, we hypothesized a M2-receptor specificity of this hypochlorite-induced enhancement. 2 The present study was performed in order to investigate whether the sympathoinhibitory response to presynaptically located M2-receptor stimulation would also be modified after exposure to hypochlorite in the rat tail artery. We applied electrical field stimulation (EFS) in order to mimic sympathetic neurotransmission. 3 EFS increased the vascular tone frequency-dependently (0.3-4 Hz). EFS-induced vasoconstriction could be attenuated by acetylcholine (30 nM-1 microM) in a concentration-dependent manner. Hypochlorite (10 and 100 microM) did not affect the sympathoinhibitory effect of acetylcholine (100 nM). 4 In conclusion, in contrast to cardiac M2-receptors, hypochlorite did not amplify the sympathoinhibitory effects of presynaptic M2-receptors. The different responsiveness between neuronal and cardiac M2-receptors to hypochlorite may be explained by the different G-protein subunits involved in the activation of the underlying signalling cascade.
Sand
C
C
Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands.
Peters
S L M
SL
Mathy
M J
MJ
Pfaffendorf
M
M
van Zwieten
P A
PA
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology; D013623:Tail / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D017661:Receptors, Presynaptic; D006997:Hypochlorous Acid