The role of adenosine in the respiratory and cardiovascular response to systemic hypoxia in the rat.

Abstract

SUMMARY1. In rats anaesthetized with Saffan we have studied the effects of the adenosine receptor antagonists, theophylline and 8-phenyltheophylline, upon the respiratory and cardiovascular responses evoked by 5 min periods of systemic hypoxia.2. In the group of animals that were to receive theophylline (15 mg kg-' i.v.), arterial 02 pressure (Pal 02) fell from 83 + 2 mmHg during air breathing to 38 + 3 or 34 + 3 mmHg during the 5th minute of two different control periods of hypoxia, while in the group that were to receive 8-phenyltheophylline (10 mg kg-' i.v.), Pa 02 fell from 83 + 1 to 53 + 2 mmHg. Neither drug significantly altered the levels of Pa, 2 reached during hypoxia. 3. During the control periods of hypoxia respiration increased, but the increase evoked at the 5th minute was significantly less than that evoked at the 2nd minute of hypoxia. This secondary waning of the hyperventilation was abolished by both drugs.4. Similarly, both drugs attenuated the tendency for the hypoxia-induced tachyeardia to wane between the 2nd and 5th minute.5. Further, both drugs substantially reduced both the hypoxia-induced fall-in arterial pressure and the increases in vascular conductance in hindlimb muscle, carotid vasculature and kidney.6. Thus, we propose that in the rat the release of adenosine by hypoxic tissues makes a major contribution to the secondary decrease in respiration and heart rate that occurs during systemic hypoxia and to the accompanying vasodilatation in muscle and fall in arterial pressure. The effects of the adenosine antagonists on the carotid and renal vasculature are more equivocal and may be partly explained as a smaller autoregulatory dilatation to a smaller fall in systemic arterial pressure.7. These results and proposals are discussed in relation to the conditions that are known to cause release of adenosine and in relation to its known effects upon the respiratory and cardiovascular systems.

Differentiation of the peripherally mediated from the centrally mediated influences of adenosine in the rat during systemic hypoxia

“…5; see Neylon & Marshall, 1991). The respiratory change evoked by adenosine was unaffected by ADA, but the cardiovascular changes were greatly reduced (Fig.…”

“…Rats were prepared for recording respiratory and cardiovascular variables as previously described (Marshall & Metcalfe, 1988a;Neylon & Marshall, 1991). Briefly, anaesthesia was induced with a halothane-oxygen mixture followed by Saffan (Pitman-Moore Ltd, Uxbridge, UK, 4 mg kg-1) given via a cannula placed in the jugular vein.…”

“…Systemic administration of the selective adenosine receptor antagonist, substantially reduced the secondary fall in ventilation, bradycardia and muscle vasodilatation (Neylon & Marshall, 1991). This led us to propose that these responses are due respectively to the actions of locally released adenosine on central respiratory neurones, on the sino-atrial node and within skeletal muscle.…”

Postnatal development of the pattern of respiratory and cardiovascular response to systemic hypoxia in the piglet: the roles of adenosine.

“…Millhorn, Eldridge, Kiley & Waldrop, 1984;Darnall, 1985;Easton & Anthonisen, 1988). Moreover, in the rat, locally released adenosine plays a part in the secondary bradycardia (Thomas, Elnazir & Marshall, 1994) and plays a major role in the muscle vasodilatation (Mian & Marshall, 1991;Neylon & Marshall, 1991;Marshall, Thomas, Turner, 1993;Thomas & Marshall, 1994;Thomas et al 1994). Thus, the aims of the present study were to establish the extent to which the respiratory and cardiovascular responses evoked by systemic hypoxia in the spontaneously breathing newborn piglet are comparable to those of the adult rat and to establish how this pattern of response changes over the postnatal period.…”

Cardiovascular/Respiratory Control

“…There is evidence for a relationship between raised body temperature and apnoea in the neonatal period (Stanton, 1984). Since the adult rat makes certain respiratory responses which resemble those of the human neonate (Neylon & Marshall, 1991), it may be useful to study this relationship in the rat. Little, however, is known about the effects of raising body temperature on ventilation in this species (Gordon, 1990).…”