Is nitric oxide really important for regulation of the cerebral circulation? Yes or no?
Since endothelium-dependent relaxation of cerebral vessels was first identified in 1980, the pivotal role of the endothelium has become evident not only in dilator responses but also in constrictor responses to various kinds of stimulation. Involvement of endothelium-derived relaxing factors (EDRFs) as well as endothelium-derived contracting factors (EDCFs) has been postulated in such vascular responses. In 1987, one of the EDRFs was determined to be nitric oxide (NO), a simple and very labile molecule, whereas endothelin composed of 21 amino acid residues was identified as one of the EDCFs in 1988. Since 1990, numerous studies which exclusively employed L-arginine analogues as specific NO synthase (NOS) inhibitors, have been undertaken to examine the role of NO in the regulation of the cerebral circulation. However, some conflicting data have emerged. The few points of consensus among the researchers may be summarized as follows: (1) NO, probably produced in the endothelium, plays an important role in the maintenance of the basal cerebral blood flow, (2) NO is not directly involved in hypoxic vasodilation, and (3) NO mediates a functional coupling of metabolism and cerebral blood flow in certain types of neural activation. Hypercapnic vasodilation and autoregulatory responses are still the main topics providing conflicting data with substantial areas of controversy. Besides ensuring appropriate experimental protocols, future studies require the precise monitoring of the degree and cellular specificity (endothelium, perivascular nerve fibers, neurons, etc.) of NOS inhibition in order to obtain concrete and reliable experimental data.
Tanaka
K
K
Department of Neurology, Keio University, Tokyo, Japan.
D002560:Cerebrovascular Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide