Mechanism of impaired myogenic response in cerebral blood vessels during posthypoxic recovery

Abstract

Cerebral blood flow autoregulation is impaired in newborn animals when a brief period of hypoxia is followed by normoxia. Because myogenic mechanisms are widely thought to be responsible for autoregulation, this study examined the effect of hypoxia and reoxygenation on the isometric mechanical function of isolated cerebral (basilar) arterial smooth muscle made to contract rhythmically and thus simulate the behaviour of arterioles. Although at rest a small amount of active tension was present in these preparations, this tension was further increased and the muscle was rendered spontaneously rhythmic by treatment with 4-aminopyridine. Reduction of bath [Formula: see text] from 120 to 25 mmHg (1 mmHg = 133.32 Pa) caused an increase in tension followed by a return towards normal tension. At this time rhythmic oscillations gradually decreased in amplitude. Restoration of normal oxygen tension caused a rapid reduction and an undershoot in tension followed by recovery to normal level. Two possible mechanisms for this undershoot, which may be due to a decrease in myogenic responsiveness and therefore of autoregulatory function, were tested. 8-Phenyltheophylline, an antagonist of adenosine receptors, caused a decrease in the inhibitory mechanical effects of adenosine (10−6–10− M). However, in the presence of 8-phenyltheophylline, there was no change in the undershoot in tension caused by reoxygenation, thus ruling out involvement of adenosine released from the vessel in smooth muscle inhibition due to hypoxia. In a separate series of experiments, the role of an electrogenic sodium pump in causing the undershoot was tested. Treatment with 5-hydroxytryptamine in a K+ -free bathing medium caused an increase in basilar artery tension. When normal potassium concentration was restored the muscle relaxed with a transient undershoot below the basal tension level. In muscle preparations pretreated with ouabain (3 × 10−6 M), the K+-induced undershoot was abolished and replaced by a transient contraction. The same concentration of ouabain decreased by 92% the tension undershoot caused by reoxygenation. These experiments rule out participation of adenosine released from the blood vessel in the loss of myogenic tone during reoxygenation. The data also indicate that reactivation of the sodium pump may be responsible to some extent for the undershoot in tone during reoxygenation of isolated canine basilar artery.