Midazolam depresses carotid body chemoreceptor activity.
BACKGROUND
Although the contribution of the gamma-aminobutyric acid (GABA) receptor system in peripheral chemosensation is unclear, immunohistochemistry has demonstrated the presence of GABA-ergic receptors in mammalian carotid bodies. We hypothesized that an activation of the carotid body GABA receptors would counteract the depolarizing effect of hypoxia.


METHODS
The carotid body with arterial supply and the carotid sinus nerve was removed en bloc from New Zealand White rabbits and placed in a perfusion chamber. The carotid body preparation was perfused via the cut common carotid artery with a modified Tyrode's solution at a rate of 3.5-4.5 ml/min with a constant pressure of 45 cmH2O. The carotid sinus nerve firing frequency (Hz) was recorded at two different oxygen tension levels during perfusion with midazolam of 1, 10 and 100 microg/l.


RESULTS
The frequency was decreased by midazolam in a dose-dependent manner (n = 8). Firing frequencies (mean +/- SEM) at the low oxygen tension level decreased from 643.13 +/- 67.2 Hz in the control to 554.5 +/- 67.7 Hz (P = 0.054 vs. control), 509.01 +/- 100.5 Hz (P < 0.012 vs. control) and 422.6 +/- 77.3 Hz (P < 0.001 vs. control) during perfusion with midazolam of 1, 10 and 100 microg/l, respectively.


CONCLUSIONS
Midazolam depresses carotid body chemoreceptor activity in a dose-dependent manner.
Kim
C
C
Department of Anesthesiology, Nippon Medical School, Sendagi, Tokyo, Japan. ckim@nms.ac.jp
Shvarev
Y
Y
Takeda
S
S
Sakamoto
A
A
Lindahl
S G E
SG
Eriksson
L I
LI
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002344:Carotid Body / Q000187:drug effects*; D002346:Carotid Sinus / Q000187:drug effects / Q000294:innervation; D002628:Chemoreceptor Cells / Q000187:drug effects*; D000860:Hypoxia / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D018079:Receptors, GABA / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D018686:Anesthetics, Intravenous; D018079:Receptors, GABA; D002245:Carbon Dioxide; D012964:Sodium; D008874:Midazolam; D011188:Potassium; D010100:Oxygen