Whether or not neurohypophyseal (NH) blood vessels actively participate in neurosecretory events or simply serve as passive conduit for hormone passage, is unknown. We observe that NH blood vessels are dynamically adjusted. Vascular conductance is actively regulated to keep blood flow constant despite changing perfusion pressure. This regulation occurs in the absence of baroreceptors and is attributed to unidentified local control mechanisms. The pattern of conductance adjustment differs from that found in other brain regions. During hemorrhage, a hyperemic component is associated with enhanced arginine vasopressin (AVP) release. We attribute the hyperemia to neurosecretion-related processes, but the factors responsible for the linkage are unknown. Because transient hyperemia is abolished by carotid sinus denervation, which does not abolish AVP release, a neural pathway separate from that regulating AVP appears to be involved. In this project, in anesthetized dogs, we will attempt to identify factors involved in neurohypophyseal blood flow (NHBF) regulation at three different levels of control.
Aim 1 focuses on vasoactive intestinal polypeptide-immunoreactive (VIP-IR) neurons, which we think provide the efferent limb of the parallel pathway. We will: 1) examine the associations of VIP-IR nerves with NH blood vessels using confocal laser microscopy, 2) determine the origin of NH VIP-IR fibers by examining the effects of lesions on the NH blood vessel/VIP-IR fiber relationships, and 3) determine the effects lesioning the suprachaismatic nucleus and carotid mini-ganglion have on NHBF and AVP responses to hemorrhagic and hypoxic stimuli.
Aim 2 focuses on nitric oxide. We will: 1) examine the associations of nitric oxide synthase (NOS) with NH blood vessels, 2) examine the effects of NOS blockade on basal NHBF and AVP release, and 3) examine the effects of NOS blockade on the the responses to hemorrhage, hypoxia and hypercarbia.
Aim 3 focuses on potassium ion (K+). Pilot data suggest K+ may serve as an ionic modulator of basal tone. We will: 1) evaluate extracellular fluid K+ [K+]o during hypotension and hypoxia, before and after baro- and chemodenervation, 2) examine the effects of drugs which prevent K+ release or inhibit Na+,K+-ATPase on NHBF responses to hypotension and hypoxia, 3) evaluate NHBF during intra-arterial KCl infusion, and 4) evaluate NHBF and [K+]. in response to neural stalk stimulation. These studies will provide new information about the role NH blood vessels play in neuroendocrine function and about their regulation.
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