Nicotine-induced skeletal muscle vasodilation is mediated by release of epinephrine from nerve terminals.
To determine the role of sympathetic innervation on nicotine-induced alterations in peripheral (hindlimb) blood flow in the pentobarbital-anesthetized dog, one hindlimb was acutely denervated and remained attached to the body by only the femoral artery and vein, whereas the contralateral limb remained innervated and intact. Measurements were made of aortic pressure, femoral artery and venous pressures, femoral artery flow, and plasma catecholamine levels during intravenous systemic infusion of nicotine. The response to nicotine (9-36 micrograms.kg-1.min-1) on the denervated side was a transient increase followed by a persistent decrease in flow and increase in vascular resistance. The response in the innervated limb was a large increase in blood flow and decrease in vascular resistance. The vasoconstrictor and vasodilator responses could be abolished by pretreatment with both propranolol and phentolamine. The vasodilator response could not be abolished by cholinergic or histaminergic receptor antagonism. Hexamethonium abolished all systemic and peripheral responses to nicotine. Desipramine selectively abolished the vasodilator response in the innervated hindlimb. The vasodilator and vasoconstrictor responses could be mimicked with systemic or local administration of epinephrine. We conclude that, in the hindlimbs of dogs, nicotine stimulates the release of epinephrine from nerve terminals and/or tissue stores to activate beta 2-adrenoceptors and promote vasodilation in skeletal muscle of innervated preparations.
Diana
J N
JN
Tobacco and Health Research Institute, University of Kentucky, Lexington 40546.
Qian
S F
SF
Heesch
C M
CM
Barron
K W
KW
Chien
C Y
CY
D000315:Adrenalectomy; D018674:Adrenergic Antagonists; D000818:Animals; D001808:Blood Vessels / Q000294:innervation; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D009132:Muscles / Q000098:blood supply*; D009411:Nerve Endings / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D010276:Parasympatholytics / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
D018674:Adrenergic Antagonists; D005730:Ganglionic Blockers; D010276:Parasympatholytics; D009538:Nicotine; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine