There is a paucity of studies regarding the regulation of vestibular blood flow (VBF), despite the possibility that vascular alterations may contribute to specific vestibulopathies. The current experiments used the Mongolian gerbil as an animal model since it provides easy surgical access to the vestibular end-organs and has been previously used for physiologic studies involving inner ear function. VBF changes were measured in the posterior semicircular canal using laser Doppler flowmetry following round window membrane (RWM) application of the nitric oxide donor 1, 3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl (spermine NONOate; SPNO) as a vasodilator. The specificity of the responses induced was tested via pretreatment with an NO scavenger, 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazonline-1-oxyl-3-oxide (carboxy-PTIO; cPTIO). cPTIO, SPNO, vehicle (control) or cPTIO/SPNO were applied to the RWM, during which blood pressure and VBF were monitored for baseline, treatment, and recovery conditions. Results showed concentration-dependent increases in flow, probably resulting from NO's vasodilatory action on local vasculature. cPTIO pretreatment was found to attenuate SPNO-induced VBF increases. These findings support a role of NO in maintaining the vestibular microcirculation.
Little is known about the physiologic regulation of the vestibular end organ blood flow. The purpose of the current study was to examine posterior semicircular canal ampulla blood flow in addition to systemic factors during intravenous infusions of calcitonin-gene related peptide (CGRP), a factor involved in the tonic regulation of blood flow. Receptors for this factor are known to be available to the vascular supply of the vestibular organs. Local blood flow using laser Doppler flowmetry and systemic parameters were monitored during infusion of CGRP. CGRP antagonists and control vehicle. The results show relatively stable vestibular blood flow (VBF), concentration-dependent decreases in systemic blood pressure, and elevations in heart rate. Pretreatment with CGRP(8-37), a specific receptor antagonist, attenuated these responses to subsequent CGRP infusions. These findings suggest a rigid regulation of VBF in the presence of a systemically active vasodilator.
Several authors have proposed that complications arising from vestibular disorders are the result of compromised circulation. The purpose of the current study was to assess the ability of flunarizine and pentoxifylline to increase peripheral vestibular blood flow (VBF), since flunarizine is a selective calcium-channel entry blocker that inhibits calcium-related contraction of smooth muscle, while pentoxifylline is a xanthine derivative that promotes microcirculation by affecting red blood cell malleability. Both of these treatment strategies have received considerable attention in clinics and laboratory, but their effects on blood flow are unclear. Changes in VBF were evaluated from the posterior semicircular canal ampulla in guinea pigs using a laser Doppler flowmeter. One group of animals was infused with pentoxifylline at concentrations of 10-40 mg/ml, while a second group was treated with 0.3-1.5 mg/kg flunarizine. VBF, blood pressure (BP) and heart rate (HR) were monitored continuously. Findings showed that pentoxifylline induced a concentration-dependent increase in VBF. In contrast, no increase in VBF occurred in response to flunarizine infusions. These studies suggest that the effectiveness of pentoxifylline in the clinical treatment of vestibular disorders may be the result of improved blood flow.
The current literature contains little information on vestibular end organ blood flow. The absence of an accepted model, difficulties applying dynamic in vivo measurement techniques and the inaccessibility of the inner ear organs contribute to the shortage of experimental findings. The purpose of the current study is to introduce the gerbil as a viable model for the in vivo study of vestibular blood flow dynamics. The potent vasoactive peptide, angiotensin III (AIII), was used to provoke blood pressure and blood flow changes. The results of this study demonstrate that viable blood flow measures may be obtained from the vestibule of the gerbil. Dose-dependent changes in blood pressure and vestibular blood flow were observed in response to high concentrations of AIII. Pretreatment with the receptor antagonist, sarthran, attenuated both blood pressure and blood flow increases in response to subsequent AIII infusions. The gerbil model offers the advantages of easily accessible and identifiable peripheral vestibular organs, as well as responsive local blood flow. Investigations using this model may provide information on the regulation of blood flow during presentation with a variety of stimulus modalities. Information from such studies may lead to development of strategies for treatment of vestibulopathies suspected to be of vascular origins.
To the authors' knowledge, these are the first in vivo descriptions of vestibular blood flow during natural stimulation. In the alert animals, VBF increased in response to NS. This increase in flow does not appear to be directly dependent on systemic blood pressure changes and indicates that the vestibular microvasculature is closely regulated.
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