Nitric oxide decreases the biological activity of norepinephrine resulting in altered vascular tone in the rat mesenteric arterial bed.
Nitric oxide (NO) reacts with catecholamines resulting in their deactivation. In this study, we demonstrated that coincubation of NO donors with sympathetic neurotransmitters decreased the amount of norepinephrine detected but not ATP or neuropeptide Y (NPY). Furthermore, we found that the ability of norepinephrine to increase perfusion pressure in the isolated perfused mesenteric arterial bed of the rat was attenuated by the incubation of norepinephrine with the NO donor diethylamine NONOate. Conversely, the vasoconstrictive ability of NPY and ATP was unaffected by incubation with NONOate. Periarterial nerve stimulation in the presence of the NO synthase (NOS) inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME) resulted in an increase in both perfusion pressure response and norepinephrine levels. This was prevented by l-arginine, demonstrating that the effects of l-NAME were indeed specific to the inhibition of NOS. To confirm that NO was not altering the release of norepinephrine from the sympathetic nerve via presynaptic activation of guanylate cyclase, we repeated the experiments in the presence of the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxaloine-one (ODQ). Unlike l-NAME, ODQ infusion did not increase norepinephrine overflow, demonstrating that modulation of norepinephrine by NO at the vascular neuroeffector junction of the rat mesenteric vascular bed is not the result of presynaptic guanylate cyclase activation. These results demonstrate that, in addition to being a direct vasodilatator, NO can also alter vascular reactivity at the sympathetic neuroeffector junction in the rat mesenteric bed by deactivating the vasoconstrictor norepinephrine.
Kolo
Lacy L
LL
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
Westfall
Thomas C
TC
Macarthur
Heather
H
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D010477:Perfusion; D011312:Pressure; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D014666:Vasomotor System / Q000502:physiology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine