Central chemoreception in the region of the ventral respiratory group in the rat.
We injected acetazolamide (AZ; 5 x 10(-6) M, 1 nl) into the region of the ventral respiratory group (VRG) of anesthetized paralyzed ventilated rats. Control injections (mock cerebrospinal fluid, n = 6, or the inactive AZ analogue 2-acetylamino-1,3, 4-thiadiazole-5-sulfon-t-butylamide, n = 6) did not increase the integrated phrenic neurogram [phrenic nerve amplitude (PNA)]. The AZ injections produced a focal region of tissue acidosis with a radius < 300-400 microns and are used as a probe for sites of central chemosensitivity. Injection location is determined by anatomic analysis. Of 22 VRG injections of AZ, 14 increased the amplitude of the PNA over 15-90 min; 8 had no effect. In 17 cases, we measured medullary tissue pH at the injection center and/or at a distant site and reaffirmed the size of the acidotic region produced by such small AZ injections. Of injections with pH electrodes within 300-400 microns of the injection center, all responders showed an acid pH; three nonresponders showed an acid pH, and one an alkaline pH. In a subgroup of five rats, at VRG sites with known respiratory effects identified by prior glutamate injection (10 nl, 100 mM), all subsequent AZ injections produced a PNA response. Simultaneous measurement of PNA and tissue pH responses at the injection center of eight rats did not show a uniform correlation in time; initially, both changed with a similar time course, but PNA recovered more quickly. We conclude that 1) the region of the VRG contains sites of ventilatory chemoreception, 2) ineffective AZ injections do produce a tissue acidosis but at sites with minimal impact on breathing, and 3) tissue pH does not uniquely represent the chemoreceptor stimulus.
Nattie
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Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA. Eugene.Nattie@Dartmouth.EDU
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D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy
D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D000086:Acetazolamide