Gender Differences in Myogenic Regulation along the Vascular Tree of the Gerbil Cochlea

Regulation of cochlear blood flow is critical for hearing due to its exquisite sensitivity to ischemia and oxidative stress. Many forms of hearing loss such as sensorineural hearing loss and presbyacusis may involve or be aggravated by blood flow disorders. Animal experiments and clinical outcomes further suggest that there is a gender preference in hearing loss, with males being more susceptible. Autoregulation of cochlear blood flow has been demonstrated in some animal models in vivo, suggesting that similar to the brain, blood vessels supplying the cochlea have the ability to control flow within normal limits, despite variations in systemic blood pressure. Here, we investigated myogenic regulation in the cochlear blood supply of the Mongolian gerbil, a widely used animal model in hearing research. The cochlear blood supply originates at the basilar artery, followed by the anterior inferior cerebellar artery, and inside the inner ear, by the spiral modiolar artery and the radiating arterioles that supply the capillary beds of the spiral ligament and stria vascularis. Arteries from male and female gerbils were isolated and pressurized using a concentric pipette system. Diameter changes in response to increasing luminal pressures were recorded by laser scanning microscopy. Our results show that cochlear vessels from male and female gerbils exhibit myogenic regulation but with important differences. Whereas in male gerbils, both spiral modiolar arteries and radiating arterioles exhibited pressure-dependent tone, in females, only radiating arterioles had this property. Male spiral modiolar arteries responded more to L-NNA than female spiral modiolar arteries, suggesting that NO-dependent mechanisms play a bigger role in the myogenic regulation of male than female gerbil cochlear vessels

Ciba Foundation Symposium 188

Producción CientíficaIn heart cells, severa! distinct kinds of transient spatial patterns of cytoplasmic calcium ion concentration ([ Ca2 + )¡) can be observed: (1) [ Ca2 + )¡ waves, in which regions of spontaneously increased [ Ca2 + ] ; propagate at high velocity (100 ¡.im/s) through the cell; (2) Ca2 + 'sparks', which are spontaneous, non-propagating changes in [ Ca2 + ] ; that are localized in small ( == 2 ¡.im) subcellular regions; and (3) evoked [ Ca2 + )¡ transients that are elicited by electrical depolarization, in association with normal excitation-contraction (E­ C) coupling. In confocal [ Ca2 + ] ¡ images, evoked [ Ca2 + ] ; transients appear to be nearly spatially uniform throughout the cell, except during their rising phase or during small depolarizations. In contrast to [Ca2 + )¡ waves and spontaneous Ca2 + sparks, evoked [ Ca2 + ] ; transients are triggered by L-type Ca2 + channel current and they are 'controlled', in the sense that stopping the L-type Ca2 + current stops them. Despite their different characteristics, ali three types of Ca2 + transient involve Ca2 + -induced release of Ca2 + from the sarcoplasmic reticulum. Here, we address the question of how the autocatalytic process of Ca2 + -induced Ca2 + release, which can easily be understood to underlie spontaneous regenerative ('uncontrolled'), propagating [Ca2 + )¡ waves, might be 'harnessed', under other circumstances, to produce controlled changes in [ Ca2 + ]¡, as during normal excitation-contraction coupling, or changes in [ Ca2 + )¡ that do not propagate. We discuss our observations of Ca2 + waves, Ca2 + sparks and normal Ca2 + transients in heart cells and review our results on the 'gain' of Ca2 + -induced Ca2 + release. We discuss a model involving Ca2 + microdomains beneath L-type Ca2 + channels, and clusters of Ca2 + -activated Ca2 + release channels in the sarcoplasmic reticulum which may form the basis of the answer to this questio

Pressure dependent diameter of female and male anterior inferior cerebellar artery.

<p>Original trace of female (A) and male (B) anterior inferior cerebellar artery in 10 µM L-NNA and Ca²⁺-free solution. Diameter in % in 10 µM L-NNA and Ca²⁺-free solution (C), % values were normalized to maximal diameter measured in Ca²⁺-free at 90 cmH₂O. 100% = 134.6 µm±6 in Ca²⁺-free at 90 cmH₂O in female animals and 132.8 µm±7.6 in Ca²⁺-free at 90 cmH₂O in male animals.</p

Calculated flow rate for brain arteries from rat and gerbil and cochlea arteries from gerbil.

<p>Male rat mid-cerebral artery (A) taken from Geary et al 1998 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025659#pone.0025659-Geary1" target="_blank">[19]</a>, male gerbil basilar artery (B) male gerbil anterior inferior cerebellar artery (C), female rat mid-cerebral artery territory branch (D), male gerbil spiral modiolar artery (E), male gerbil radiating arteriole (F). Green bars represent estimated physiological pressure range for each vessel according to which active and passive slope were calculated. Slope is given in µl/min –cmH₂O. For active slope diameter was obtained in 10 µM L-NNA, for passive slope diameter was obtained in Ca²⁺-free solution.</p

Myogenic tone development along the cochlear vascular tree in male and female gerbil.

<p>The myogenic tone at the reference pressure of 60 cmH₂O was 4±2% in male (n = 5) and 4±1% in female (n = 4) basilar arteries (A), 7±1% in male (n = 6) and 4±1% in female (n = 7) anterior inferior cerebellar arteries (B), 17±4% in male (n = 6) and 6±3% in female (n = 7) spiral modiolar arteries (C), and 16±2% in male (n = 4) and 15±3% in female (n = 4) radiating arterioles (D). “*” indicates statistical significance (p<0.05) by ANOVA (2-factor repeated-measures).</p

Diameter and myogenic tone in female rat mid-cerebral artery territory branch.

<p>Original trace of female rat mid-cerebral artery territory branch in 10 µM L-NNA and Ca²⁺-free solution (A). Calculated myogenic tone in %, n = 1 (B).</p

Pressure dependent diameter of female and male radiating arteriole.

<p>Original trace of female (A) and male (B) radiating arteriole in 10 µM L-NNA and Ca²⁺-free solution. Diameter in % in 10 µM L-NNA and Ca²⁺-free solution (C), % values were normalized to maximal diameter measured in Ca²⁺-free at 80 cmH₂O. 100% = 52.4 µm±3.3 in Ca²⁺-free at 90 cmH₂O in female animals and 53.2 µm±1.7 in Ca²⁺-free at 90 cmH₂O in male animals.</p