Nitric oxide and hypertension: not just an endothelium derived relaxing factor!
The importance of endothelial nitric oxide (NO) generation in sustaining a tonic systemic vasodilatation is well established. Inhibiting NO production produces hypertension in animals and in humans and not surprisingly there has been considerable interest in establishing whether deficiencies of endothelial NO pathway activity are implicated in the aetiology of essential hypertension. The results of these investigations have been inconsistent with some suggestion that observed deficiencies of both basal and stimulated endothelial NO generation in hypertensive subjects may be an effect rather than the cause of raised arterial pressure. It is increasingly recognised that neuronal production of NO also influences cardiovascular homeostasis through its action as a neuromodulator within the autonomic nervous system. Overall NO has been shown to have sympatho-inhibitory and vagotonic effects, acting by both central and peripheral mechanisms. Sympathetic overactivity, coupled with the permissive role of a depressed level of baroreflex mediated cardiac vagal control, may play a significant role in the genesis of human hypertension. Early work in hypertensive rats suggests that neuronal NO production is impaired at a number of key central sites concerned with autonomic cardiovascular regulation. This data is consistent with the pattern of autonomic dysfunction observed in human hypertension. The possibility that neuronal rather than endothelial production of NO might play a significant role in the aetiology of essential hypertension is a promising area for future human research.
Chowdhary
S
S
Department of Cardiovascular Medicine, University of Birmingham, Birmingham, UK. S.Chowdhary@bham.ac.uk
Townend
J N
JN
D001341:Autonomic Nervous System / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*
D009569:Nitric Oxide