Cerebral Circulation and Histamine: 1. Participation of Vascular H ₁ - and H ₂ -Receptors in Vasodilatatory Responses to Carotid Arterial Infusion

We examined the cerebral circulatory effects of intra-carotid infusion of histamine or its receptor agonists in anesthetized rats. Cerebral blood flow was measured by two methods: an intracarotid 133 Xe clearance technique and tissue sampling after systemic administration of the diffusible tracer, [ 14 C]iodoantipyrine. Brain metabolic responses were estimated by the 2-deoxyglucose method and tissue sampling. Intracarotid infusion of histamine when the blood-brain barrier was intact did not increase cerebral blood flow. Following disruption of the blood-brain barrier by carotid injection of hypertonic urea, histamine evoked dose-dependent increases ( 133 Xe clearance method) in cerebral blood flow to a maximum of 50% (20 μg min −1 kg −1 ); histamine produced increases in blood flow to areas supplied by the internal carotid artery, e.g., thalamus and parietal cortex ([ 14 C]iodoantipyrine method). Both classes of histamine receptors (H 1 and H 2 ) participated in mediating increases in cerebral blood flow after blood-brain barrier opening. Mepyramine (H 1 -antagonist) and metiamide (H 2 -antagonist) attenuated blood flow responses to histamine infusion ( 133 Xe clearance method); metiamide was the more effective blocking agent. Pyridylethylamine (H 1 -agonist) and dimaprit (H 2 -agonist) both caused increases in regional cerebral blood flow ([ 14 C]iodoantipyrine method). Histamine infusion after blood-brain barrier opening did not increase cerebral glucose consumption. We suggest that increases in cerebral blood flow produced by histamine are the result of stimulation of vascular H 1 - and H 2 -receptors, rather than a secondary response to metabolic activation.