Analysis of the cardiovascular changes induced in the rat by graded levels of systemic hypoxia.

1. In rats anaesthetized with Saffan, we have further analysed the respiratory, cardiac and regional vascular responses induced by 3 min periods of graded hypoxia (breathing 15, 12, 8 or 6% O2 in N2). 2. Frequently, hypoxia evoked an episode, lasting 1‐1.5 min, of tachycardia, renal and mesenteric vasoconstriction and skeletal muscle vasodilatation. The tachycardia and muscle vasodilatation persisted after vagotomy indicating they were not initiated by pulmonary stretch receptors secondary to hyperventilation. We propose that such episodes represented the cardiovascular components of the alerting‐defence response initiated by activation of the brain stem defence areas by peripheral chemoreceptors. 3. Each of these episodes was superimposed upon gradual hyperventilation, tachycardia, fall in arterial pressure and vasodilatation in renal, mesenteric and muscle circulation the magnitudes of which at 2 min were generally graded with the level of hypoxia. In the 3rd minute, respiration and heart rate tended to wane below control levels. 4. Vagotomy had little effect on the heart rate changes and only slightly reduced the peripheral vasodilatation allowing the conclusion that the gradual tachycardia and peripheral vasodilatation was not a reflex initiated by pulmonary stretch receptors. 5. Guanethidine given after vagotomy abolished the tachycardia indicating it was sympathetically mediated; possible initiating factors are discussed. But the secondary bradycardia persisted indicating it reflected the direct effect of hypoxia on cardiac pacemaker tissue. 6. The peripheral vasodilatation persisted after guanethidine or phentolamine indicating it was mainly attributable to the local vasodilator effects of tissue hypoxia. 7. It is proposed that the components of the alerting response are an integral part of the response to systemic hypoxia. Further, that in the rat this response is superimposed upon, but may be overcome by the direct effects of hypoxia on peripheral vasculature, heart and central nervous system.