Abstract

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

Highlights

  • Mammals have developed different mechanisms to maintain oxygen delivery to cells in response to environmental or disease modifications that interfere with the gas flow

  • Those studies found that guinea pigs hyperventilated in response to hypercapnia with an increase in minute ventilation equal to, or higher than that observed in rats, showing that central chemoreceptors, that mediate most of the ventilatory response to hypercapnia (Alarie and Stock, 1988; Guyenet and Bayliss, 2015), as well as the brainstem integration mechanisms are well preserved

  • Plethysmography data show that guinea pig and rat ventilatory parameters breathing air are similar but guinea pigs hyperventilate only in response to intense hypoxic test (7% O2) not showing ventilatory changes when breathing 12 or 10% O2 atmosphere

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Summary

Introduction

Mammals have developed different mechanisms to maintain oxygen delivery to cells in response to environmental or disease modifications that interfere with the gas flow Among those mechanisms are the carotid body (CB) chemoreceptors, a specialized cell system able to detect physiological hypoxia and generate homeostatic responses. Fernández et al (2003) using the Dejours-type test, found that a short period of pure O2-breathing inhibited ventilation in guinea pigs comparable to that in the cat and higher than in the rat, suggesting that the guinea pig CB was sensitive to and silenced by pure O2 followed by a decrease in ventilation Those studies found that guinea pigs hyperventilated in response to hypercapnia with an increase in minute ventilation equal to, or higher than that observed in rats, showing that central chemoreceptors, that mediate most of the ventilatory response to hypercapnia (Alarie and Stock, 1988; Guyenet and Bayliss, 2015), as well as the brainstem integration mechanisms are well preserved

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