This is a proposal to study the constrictor and dilator neuroeffector control mechanisms of the cerebral and extracerebral cranial circulation. The specific aims include: (1) characterization of the "unusual" alpha-adrenoceptor found in the rabbit basilar artery, (2) testing the hypothesis that the dilator innervation to some cranial blood vessels involves two transmitters - acetylcholine and possibly vasoactive intestinal polypeptide and that this dilator effect is mediated by the tunica intima, (3) comparing the control of large pial arteries and their tributaries as small as 70 u OD, (4) elucidating the efferent vasodilator neural pathways to cerebral and extracerebral blood vessels, (5) determining the distribution of the dilator innervation within the head, (6) characterizing the significance of the increased level of the choline acetyl-transferase found in anterior facial veins, (7) determining whether the sites of transition of alpha-adrenoceptor characteristics, similar to those that occur along the vertebral and internal carotid artery are found at other embryological significant sites and whether they relate to other receptor types. These studies will be pursued in the cat and rabbit utilizing a variety of techniques (1) catecholamine histofluorescence, immunohistochemistry of polypeptides and transmission electron microscopy (2) drug induced neurogenic constriction and dilation elicited in vitro by electrical field stimulation and their pharmacological analysis using conventional as well as resistance vessel myographs (3) measurements of acetylcholine, norepinephrine, choline acetyltransferase activity, high affinity choline and specific neuronal norepinephrine uptake and (4) surgical denervation procedures. These studies should further our knowledge of the unique neural control systems of cerebral and other cranial vascular beds and provide knowledge that might lead to a better understanding of their role and the possibilities for pharmacological manipulation.
NIH ExPorter
NIH ExPorter