Neurohumoral Regulation of the Cerebral Circulation

Abstract

The cerebral circulation is regulated by chemical stimuli, metabolic factors, perfusion pressure, and nerves. However, the role of certain neurohumoral mechanisms in the regulation of cerebral blood flow remains rather controversial (1, 2). The unique characteristics of this regional circulation could provide a partial explanation for the previously reported divergent roles of neurohumoral control mechanisms. For instance, arteries and large arterioles are important resistance vessels, in contrast to most other circulations (2, 3). Second, most brain vessels possess a blood-brain barrier that limits access of circulating agents to the brain parenchyma (2). Third, neurotransmitters could escape from the synaptic region and accumulate in the cerebrospinal fluid (CSF), thereby providing a mechanism for the transport of these substances to distant cerebral targets. While there are many stimuli for the regulation of the cerebral circulation, the arterial PCO₂ is one of the most important (2). Hypocapnia results in arterial constriction and reduced cerebral blood flow, whereas hypercapnia causes profound arterial dilation and increased cerebral blood flow (2). However, this review will not describe the cerebrovascular effects of inorganic stimuli such as PCO₂, PO₂, or pH. This review will focus on local humoral control of a paracrine-autocrine nature and on selected novel (vasopressinergic, opioid) and classical (sympathetic, cholinergic) neural-humoral stimuli for the control of the cerebral circulation. Due to the voluminous literature on the subject and the intended nature of a minireview, local humoral control of cerebral hemodynamics, although of intense interest, can be presented in a general, overview fashion only.

Paracrine-Autocrine Stimuli

The contributions of prostanoids to the regulation of cerebral hemodynamics in adult animals are the subject of considerable controversy. Indomethacin has been reported to reduce cerebral blood flow and abolish cerebrovascular dilation in response to hypercapnia in adult baboons and gerbils (4, 5). Conversely, others have found that indomethacin, at doses that block cerebral dilator responses to exogenous arachidonic acid, does not alter cerebral blood flow, pial arterial diameter, or responses of cerebral arterioles to hypercapnia in adult cats or rabbits (6, 7).