Camp. Biorlrtvn. P/~~sio/. Vol. 109A. No. 3. pp. 675-680, 1994 Copyright c 1994 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0300-9629/94 57.00 + 0.00 Pergamon 0300-9629(94)00096-4 Ventilatory response to severe acute hypoxia in guinea-pigs and rats with high hemoglobin-oxygen affinity induced by cyanate M. Rivera-Ch, F. Lebn-Velarde, L. Huicho and C. Monge-C. Departamento de Ciencias Fisiolbgicas and Instituto de Investigaciones de Altura, Laboratorio de Biofisica, Universidad Peruana Cayetano Heredia, Lima, Peru Baseline ventilation, hemoglobin concentration (Hb) and P50 were significantly lower in guinea-pigs than in rats. Chronic sodium cyanate (NaOCN) administration did not significantly increase hemoglobin concentration in either guinea-pigs or rats. It decreased the P50 significantly less in guinea-pigs than in rats. The high Hb-O2 affinity experimentally induced did not modify the hypoxic ventilatory response (HVR) of guinea-pigs and rats. At the same level of acute hypoxia, HVR was significantly lower in NaOCN guinea-pigs than in NaOCN rats. Guinea-pigs, genotypically adapted animals to high altitude, displayed relatively minor ventilatory and Hb-O2 affinity changes to NaOCN, and a relatively minor HVR to acute hypoxia. They probably use tissue and biochemical adaptive mechanisms, in addition to their limited extracellular responses to successfully tolerate ambient hypoxia. Key words: Ventilation; Hypoxia; Guinea-pig; Hemoglobin-oxygen affinity; Cyanate; Altitude; Genetic adaptation; Hypoxic ventilatory response. Comp. Biochem. Physiol. 109A, 675-680, 1994. Introduction The guinea-pig (Cauiu porcellus), originally from the Andes, is a mammal considered as genotypically adapted to high altitude. This viewpoint rests on the consistent finding of two characteristics: a high hemoglobin oxygen affinity (low P50) and the develop- ment of moderate erythrocytosis when exposed to chronic hypoxia (Turek et al., 1980). These characteristics remain fixed at sea level. Since the ventilatory rate plays an im- portant role in maintaining the adaptive zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM Correspondence to : M. Rivera-Ch, Departamentode Ciencias Fisiohjgicas,Laboratorio de Biofisica, Universidad Peruana Cayetano Heredia, Lima 100, Peru. Fax (51-14)823435. Received 2 February 1994; accepted 20 May 1994. capacity of high altitude mammals and birds (Monge-C and Le6n-Velarde, 199 l), it was considered important to investigate the hypoxic ventilatory response (HVR) in guinea-pigs and compare it with HVR of the rats. The rat can be acclimatized to high altitude, but it is not genotypically adapted to the hypoxic environment. In small mammals, an attenuated (blunted in the literature) respiratory re- sponse to acute hypoxia has been shown in hypoxia acclimatized mice (Monge-C, 1988) as well as in rats (Barer et al., 1976). A higher basal ventilatory rate (30% higher than that of control animals) has been shown in guinea-pigs acclimated at a barometric pressure of 430 Torr for 11-15 weeks (Blake and Banchero, 1985). In con- trast, this same study showed that acute breathing of a gas mixture containing 675