PubMed Health⌕ Search

Biomedical subjects

R Iturriaga

Publications and source records attributed to R Iturriaga.

At least 19 recordsLinked to original sources
PubMed1996

Dissociation of hypoxia-induced chemosensory responses and catecholamine efflux in cat carotid body superfused in vitro.

1. To examine the correlation between chemosensory response and dopamine release induced by hypoxic stimulation, we studied carotid bodies excised from anaesthetized cats. 2. The carotid bodies with their carotid (sinus) nerves were superfused in vitro with modified Tyrode solution (pH 7.40, at 37.5 degrees C) equilibrated with 20 or 100% O2. The PO2 of the superfusing channel was monitored polarographically. The frequency of chemosensory discharges (fx) was recorded from the whole carotid nerve. Catecholamine (CA) efflux-mostly consisting of dopamine-was measured by high-speed chronoamperometry, through Nafion-coated carbon electrodes placed on the carotid body tissue. Chemosensory stimulation was induced by intrastream injections of NaCN, by superfusion with 100% N2-equilibrated saline (lowering PO2 to 25-40 Torr) or by flow interruption. 3. Low doses of NaCN increased fx, but had no measurable effect on CA efflux, while larger doses produced fast increases in fx, preceding delayed and prolonged increases in CA efflux. Repeated injections of NaCN, still increasing fx, gave reduced CA effluxes. 4. Switching to hypoxic superfusion for 6-8 min produced large and fast fx increases, but delayed and prolonged augmentations of CA efflux. 5. Administration of three to four boluses of dopamine (7-15 micrograms; augmenting CA concentration by up to 35 microM) initially decreased fx, after which hypoxic stimulation resulted in enhanced and faster CA effluxes, without changing the speed and intensity of chemosensory responses. 6. Flow interruptions induced fast increases in fx and delayed increases in CA efflux. Repeated flow interruptions produced similar increases in fx but progressively attenuated CA effluxes. 7. Our results suggest that CA efflux is not essential for hypoxia-induced chemosensory excitation in the cat carotid body. They also suggest the presence of two pools of releasable CAs in the carotid body, one of slow turnover and release, and another of recently incorporated dopamine and fast release, both pools being rapidly depleted by repeated stimulation of the carotid body.

Animals↗
PubMed1996

Adaptation to hypercapnia vs. intracellular pH in cat carotid body: responses in vitro.

The hypotheses that the chemosensory discharge rate parallels the intracellular pH (pHi) during hypercapnia and that the initial change in pHi (delta pHi) is always more than the stead-state delta pHi were studied by using cat carotid bodies in vitro at 36.5 degrees C in the absence and presence of methazolamide (30-100 mg/l). Incremental acidic hypercapnia was followed by an incremental initial peak response and a greater adaptation. A given acidic hypercapnia elicited a rapid initial response followed by a slower adaptation; isohydric hypercapnia produced an equally rapid initial response but of smaller magnitude that returned to near-baseline level; alkaline hypercapnia induced a similar rapid initial response but one of still smaller magnitude that decreased rapidly to below the baseline. Methazolamide eliminated the initial overshoot, which also suggested involvement of the initial rapid pHi in the overshoot. These results show that the initial delta pHi is always greater than the steady-state delta pHi and during hypercapnia. Also, the steady-state chemoreceptor activity varied linearly with the extracellular pH, indicating a linear relationship between extracellular pH and pHi.

Adaptation, Physiological↗
PubMed1994

Effects of dopaminergic blockade upon carotid chemosensory activity and its hypoxia-induced excitation.

The effects of domperidone, antagonist of D2 receptors, on arterial chemoreceptor activity were studied in spontaneously breathing and pentobarbitone anesthetized cats, in which recordings of chemosensory impulse activity were obtained simultaneously from both cut carotid (sinus) nerves. Intravenous injections of domperidone 50 micrograms/kg produced a maintained increase in the basal frequency of chemosensory discharges, after which hyperoxic tests (breathing 100% O2 for 30 s) evoked larger falls in the rate of chemosensory impulses. Chemosensory responses evoked by hypoxic hypoxia (100% N2 tests) and by cytotoxic hypoxia (i.v. injections of NaCN) reached higher impulse rates after domperidone treatment. The effects of domperidone reveal that a resting release of dopamine from glomus cells maintains a low level of basal chemosensory activity under normoxic conditions. Domperidone turns off such restraining dopaminergic control and enhances the transient chemosensory responses to hypoxic stimuli. Present data support a modulatory role for dopamine within the chemoreceptor process, but not its participation as excitatory transmitter between glomus cells and sensory nerve endings.

Animals↗
PubMed1994

Testing the metabolic hypothesis of O2 chemoreception in the cat carotid body in vitro.

It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the high-energy state without net production of ATP. The metabolic hypothesis for O2 chemoreception in the carotid body (CB) predicts that 1) oligomycin should diminish O2 consumption and attenuate O2 chemoreception and 2) uncouplers should reverse the effect of oligomycin by increasing O2 consumption without restoring O2 chemoreception. These predictions were tested by simultaneously measuring CB chemosensory discharge from the sinus nerve and the rate of tissue O2 disappearance (dPO2/dt) during interruption of perfusate flow in perfused-superfused cat CB preparations (n = 9). O2 consumption was calculated from dPO2/dt. Flow-interruption responses were measured before and after oligomycin (1-microgram bolus) and subsequently after dinitrophenol (50 microM). Chemosensory responses to bolus injections of hypercapnic Tyrode solution, cyanide, or nicotine were also tested periodically. Oligomycin diminished dPO2/dt from -2.67 +/- 0.30 to -2.02 +/- 0.19 (SE) Torr/s (P < 0.004, paired t test) and reduced the maximal sensory response from 196 +/- 43 to 124 +/- 12 impulses/s (P < 0.002, paired t test) while augmenting the initial response to CO2. Dinitrophenol reversed the metabolic depressant effect of oligomycin but further suppressed the chemosensory response. These results confirm the above predictions and strengthen the metabolic hypothesis for O2 chemoreception in the CB.

2,4-Dinitrophenol↗
PubMed1994

Phrenic nerve activity during artificial ventilation at different body temperatures and its relationships with carotid chemosensory activity.

While the chemoreceptor discharges of carotid bodies in vitro are highly dependent on temperature, these chemoreceptors in situ contribute only moderately to the ventilatory adjustment to changing body temperature (Tb), probably because of the concomitant and reverse changes in natural chemoreceptor stimuli in closed-loop preparations. Accordingly, we studied the frequency of carotid chemosensory discharge (fx) and the phrenic integrated electroneurogram (IENGph) in pentobarbitone anesthetized cats, paralyzed with alcuronium and artificially ventilated, at three steady-state levels of Tb (35.5, 37.5 and 40.2 degrees C), modifying the frequency and volume of the ventilator to maintain PETCO2 within normal range. While fx increases along with Tb when PETCO2 is allowed to fluctuate freely, its mean basal value was not consistently different at the three Tb's studied under controlled conditions. The amplitude of IENGph was reduced and the frequency of phrenic inspiratory cycles was increased as Tb was raised from 35.5 to 37.5 degrees C and then to 40.2 degrees C. Brief 100% O2 inhalations and i.v. injections of dopamine produced minimal depressions of IENGph amplitude in hypothermia, but pronounced although similar depressions in normothermia and hyperthermia. i.v. injections of NaCN augmented fx and IENGph in dose related manner, and the relationships between both variables showed larger changes in IENGph at the hypothermic and normothermic conditions when expressed in absolute terms, but not when expressed in relative terms. Thus, the chemosensory input is not consistently modified by thermal levels under controlled ventilatory conditions, but the chemosensory drive of the ventilatory output is less pronounced in hypothermia. The chemosensory input is similarly affected by varying degrees of cytotoxic hypoxia at different Tb's, but the ventilatory output is less vigorously increased in hyperthermia, pointing to a decreased reflex gain in that condition.

Animals↗