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 ¹³³Xe clearance technique and tissue sampling after systemic administration of the diffusible tracer, [¹⁴C]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 (¹³³Xe 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 ([¹⁴C]iodoantipyrine method). Both classes of histamine receptors (H₁ and H₂) participated in mediating increases in cerebral blood flow after blood-brain barrier opening. Mepyramine (H₁-antagonist) and metiamide (H₂-antagonist) attenuated blood flow responses to histamine infusion (¹³³Xe clearance method); metiamide was the more effective blocking agent. Pyridylethylamine (H₁-agonist) and dimaprit (H₂-agonist) both caused increases in regional cerebral blood flow ([¹⁴C]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 H₁- and H₂-receptors, rather than a secondary response to metabolic activation.