The vasoactive role of nitric oxide: physiological and morphological aspects

Nitric oxide (NO) participates in the control of the cardiovascular system where two constitutive isoforms of NO-synthase were discovered: endothelial and neuronal. Both isoforms were observed in various cells, however, endothelial NO-synthase is predominantly present in the endothelium. Injury of the endothelium disturbs the balance between vasodilation and vasoconstriction and triggers different pathological alterations. In addition, whereas the intact endothelium protects vascular smooth muscle from oxidative attack, intervention in the vascular wall integrity increases the concentration of vascular superoxides, thus disturbing the effects of NO. To preserve NO-mediated vasorelaxation, different reserve mechanisms have developed. In case of damage of some endothelial receptor type, vasodilation could be ensured by activation of some other type of the present receptors. Moreover, morphological evidence demonstrated that both isoforms of NO-synthase were expressed also in smooth muscle cells and functional studies revealed that different pathological interventions in endothelial function (such as oxidative stress or hypertension) were associated with NO generation in the vascular media. In this case, the generation of NO by vascular smooth muscle may represent a physiologically relevant compensation of endothelial NO deficiency. Whereas long-term inhibition of endothelial NO-synthase resulted in an unequivocal pattern of cardiovascular changes, inhibition of neuronal NO-synthase led to opposite effects, suggesting a specific position of neuronal NO-synthase in the regulation of cardiovascular tone. The specificity of endothelial or neuronal NO function seems to be related to a particular circulatory area and it is presumably determined by mutual interactions with other regulatory systems (sympathoadrenergic, renin-angiotensin, etc.).