Effect of a Ca2+ entry blocker, nilvadipine, on hearing disturbances and equilibrium dysfunction caused by microcirculatory disorders of the rat inner ear.
We evaluated the effects of Ca2+ entry blockers, nilvadipine and flunarizine, on microcirculatory disorders of the inner ear and on blood flow in the inner ear of rats. Under sodium pentobarbital anesthesia, the middle ear was opened by a ventrolateral approach. A green light (wave length 540 nm) was applied to the cochlea or the vestibule to induce a hearing disturbance or equilibrium dysfunction as a result of inner ear microcirculatory disorders, while rose bengal solution was infused intravenously. In a hearing disturbance model, a compound cochlear nerve action potential was recorded by electrocochleography every minute after the beginning of illumination. The sound stimulus was an 8 kHz sine wave 100 dB normal hearing level. The action potential was calculated 128 times. The action potential disappeared about 12 min after the beginning of illumination. In another model of equilibrium dysfunction, the photoillumination was applied for 40 min under the infusion of rose bengal. The behavior of rats was observed in the swimming test and nystagmus was recorded 24 h after the completion of photoillumination. In a separate experiment, blood flow in the inner ear was measured with a laser Doppler flowmeter under sodium pentobarbital anesthesia. In this study, both nilvadipine and flunarizine prolonged the time required for complete suppression of the action potential, prevented equilibrium dysfunction in the swimming test and reduced the occurrence of nystagmus. Flunarizine significantly increased inner ear blood flow and nilvadipine failed to decrease blood flow in the inner ear, despite a reduced systemic blood pressure. In conclusion, Ca2+ entry blockers may prevent microcirculatory disorders of the inner ear in rats.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Kohno
Y
Y
Asai
Y
Y
Uematsu
T
T
Nakashima
M
M
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects; D007758:Ear, Inner / Q000098:blood supply*; D005444:Flunarizine / Q000494:pharmacology; D006311:Hearing Disorders / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012678:Sensation Disorders / Q000503:physiopathology; D014466:Ultraviolet Rays
D002121:Calcium Channel Blockers; C035100:nilvadipine; D009543:Nifedipine; D005444:Flunarizine