Parasympathetic cholinergic control of cerebral blood flow in dogs.

SUMMARY We studied the effects of cholinergic receptor activation on cerebral blood flow in dogs anesthetized with chloralose. Continuous measurements of cerebral blood flow, arterial and cerebral spinal fluid pressure, heart rate, and respiratory carbon dioxide tension were made during parasympathetic nerve stimulation and during intraarterial infusion of acetylcholine. Multiple samples of arterial and cerebral venous blood were taken before, during, and after cholinergic vasodilation and analyzed for oxygen tension, carbon dioxide tension, and pH. Dose-response curves obtained by intra-arterial infusion of acetylcholine at 0.27-1,080 /ig/min and stimulation frequency-response curves obtained by excitation of the major petrosal nerve at 2-40 Hz demonstrated a dose or frequency-dependent cerebral vasodilation. The maximum cerebral vasodilation (171% of control flow) was obtained with an acetylcholine infusion of 1,080 /xg/min. During infusion of 27 /tg of acetylcholine/min arterial blood gases showed little or no change and thus could not have produced the observed change in cerebral blood flow. The changes in cerebral venous blood were all consistent with the observed increase in cerebral blood flow; oxygen tension rose from 30.4 to 36.0 mm Hg, carbon dioxide tension fell from 45.7 to 42.3 mm Hg, and pH rose from 7.342 to 7.360. Ipsilateral stimulation of the major petrosal nerve at 10 Hz, with a 3-msec pulse duration and 60-second stimulation period, produced an increase in cerebral blood flow to 111% of control flow. Cholinergic receptor blockade with atropine (1 mg/kg, i.v.) completely eliminated the cerebral vasodilation produced by acetylcholine infusion at 27 figlmin and significantly reduced the vasodilation resulting from major petrosal nerve stimulation. We conclude that the cerebral circulation has the capacity for significant cholinergic vasodilation. THE ABUNDANT anatomical evidence demonstrating the existence of nerve fibers on the cerebral vessels has recently been reviewed. 1 The sympathetic autonomic component of this innervation has been shown to have the capacity for marked cerebral vasoconstriction via an aadrenergic receptor mechanism. 2 - 3 A parasympathetic cerebral vasodilator mechanism was suggested by early workers when they observed pial vessel dilation in response to cranial nerve stimulation. 4 More recently, intravertebral atropine was shown to suppress the dilation resulting from inhalation of 5% CO2, 5 and intravertebral neostigmine enhanced cerebral vasodilator reactivity to CO2. (i Atropine was also shown to eliminate "autoregulatory dilation" in unanesthetized rabbits. 7 Each of these observations is consistent with a parasympathetic cholinergic vasodilator mechanism for the cerebral circulation. None of these studies demonstrates a parasympathetic cholinergic increase in cerebral blood flow. A cholinergic vasodilator mechanism to compliment the adrenergic vasoconstrictor mechanism has, therefore, not been clearly defined for the control of cerebral blood flow. In the present study, parasympathetic nerve stimulation and intra-arterial infusion of a cholinergic agonist, acetylcholine, were used to test for a possible parasympathetic cholinergic cerebral vasodilator mechanism.