Cerebral circulation and histamine: 1. Participation of vascular H1- and H2-receptors in vasodilatory responses to carotid arterial infusion.

We examined the cerebral circulatory effects of intra-carotid infu­ sion of histamine or its receptor agonists in anesthetized rats. Cerebral blood flow was measured by two methods: an intracarotid I:l3Xe clearance technique and tissue sampling after systemic administration of the diffusible tracer, [14C]iodoantipyrine, Brain metabolic responses were estimated by the 2deoxyglucose 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 hyper­ tonic urea, histamine evoked dose-dependent increases (J33Xe clearance method) in cerebral blood flow to a maximum of 50% (20 JLg minkg-); his­ tamine 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 (HI and Hz) participated in mediating in­ creases in cerebral blood flow after blood-brain barrier opening. Mepyramine (HI-antagonist) and metiamide (Hz-antagonist) attenuated blood flow responses to histamine infusion C33Xe clearance method); metiamide was the more effec­ tive blocking agent. Pyridylethylamine (HI-agonist) and dimaprit (Hz-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 HIand Hzreceptors, rather than a secondary response to metabolic activation.