Neurogenic vasodilation in rabbit hindlimb mediated by tachykinins and nitric oxide.
We investigated the role of nitric oxide (NO) in the mediation of nerve stimulation-induced vasodilation in skeletal muscle. Hindlimb blood flow and vascular resistance were measured in pentobarbital-anesthetized, paralyzed, and guanethidine-treated rabbits. Centrifugal electrical stimulation of the sciatic nerve bundle induced reproducible, frequency-, voltage-, and pulse duration-dependent decrements in vascular resistance. The tachykinin antagonist CP-96,345 (1 mg/kg intravenously, i.v.) attenuated the vasodilation induced by intraarterially (i.a.) administered substance P but not by adenosine. Furthermore, CP-96,345 attenuated the decrease in vascular resistance in response to nerve stimulation, from 22.9 +/- 3.2 to 4.5 +/- 4.1% of control resting resistance (p < 0.005), without affecting basal vascular resistance. An inhibitor of NO formation, N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.v.), increased vascular resistance from 6.1 +/- 0.5 to 9.1 +/- 1.2 resistance units (p < 0.05) and significantly attenuated the vascular response to i.a. administered substance P but not adenosine. Finally, nerve stimulation-induced reduction in vascular resistance was attenuated by L-NAME, from 22.6 +/- 2.7 to 7.0 +/- 1.0% of control (p < 0.001). These findings suggest that tachykinins and NO are involved in mediation of vasodilation in response to the present type of nerve stimulation. The data are consistent with the hypothesis that NO is produced subsequent to neural release of tachykinin-type transmitter(s).
Gustafsson
L E
LE
Department of Physiology and Pharmacology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Persson
M G
MG
Wei
S Z
SZ
Wiklund
N P
NP
Elias
Y
Y
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D006614:Hindlimb; D008297:Male; D009132:Muscles / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology*; D011817:Rabbits; D012584:Sciatic Nerve / Q000502:physiology; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D015320:Tachykinins; D009569:Nitric Oxide