Capsaicin-induced release of substance P increases cochlear blood flow in the guinea pig.
Physiological evidence from several studies suggests that endogenous vasoactive peptides, such as substance P (SP), and their respective receptor populations may participate in the mechanisms that govern the autoregulatory capacity of the cochlear vascular system. However, these studies do not provide evidence regarding the origin or mechanism of action of SP. Capsaicin sensitivity has been used as a marker for sensory neurons, and the release of SP following capsaicin treatment suggests a sensory transmitter role for SP. The present investigation examines the relationship between the capsaicin-sensitive sensory neurons and SP in the regulation of cochlear blood flow (CBF). In 75 pigmented guinea pigs, the cochlea was surgically exposed and a laser Doppler flowmeter probe placed on the bony surface of the first turn to monitor CBF. Capsaicin solutions (2 microliters, 0.01%, 0.001% and 0.0001%) applied to the round-window membrane (RWM) resulted in a dose-related CBF increase, without change in the systemic blood pressure. This effect could be inhibited by application of a specific SP receptor antagonist, [D-Pro2,D-Trp7,9]-SP, after which none of the capsaicin concentrations used induced a change in CBF. Moreover, after RWM application of 50 nmol/2 microliters of SP there was a significant increase in CBF. No CBF change was observed with the lower concentrations of 10 nmol SP or 100 pmol SP. These results indicate a role of SP in CBF regulation and give indirect evidence that SP is released from capsaicin-sensitive primary sensory neurons.
Vass
Z
Z
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506.
Nuttall
A L
AL
Coleman
J K
JK
Miller
J M
JM
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects* / Q000294:innervation; D005260:Female; D006168:Guinea Pigs; D006706:Homeostasis; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology
D013373:Substance P; C032132:substance P, prolyl(2)-tryptophan(7,9)-; D002211:Capsaicin