Nitric Oxide

Endogenous production of oxides of nitrogen by mammals was first suggested by Mitchell and colleagues in 1916 [2]. However, it was not until

CEREBRAL BLOOD FLOW: PHYSIOLOGY AND MEASUREMENT TECHNIQUES

ACh Bk ADP ET-1 AVP SP

Shear stress

ACh Bk ADP ET-1 AVP SP

Shear stress

Fig. 17.1. Biosynthesis of nitric oxide. The (constitutive) endothelial isoform of NOS is activated by the influx of calcium induced by shear stress or the binding of agonists to their receptors on the surfaces of endothelial cells. Endothelial NOS uses molecular oxygen and several cofactors to convert the amino acid L-arginine to NO, forming L-citrulline as a by-product. The molecular chaperone HSP90 is known to facilitate this reaction. Abbreviations for Figs 17.1 and 17.2 (see text for cofactor abbreviations): Ach, acetylcholine; ADP, adenosine diphosphate; AVP, arginine vasopressin; BK, bradykinin; cGMP, cyclic-3'5'-guanosine monophosphate; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; GC, guanylate cyclase; GTP, guanosine triphosphate; HSP90, heat shock protein 90; L-arg, L-arginine; MLC, myosin light-chains; NO, nitric oxide; PKG, protein kinase G; SP, substance P.

Fig. 17.1. Biosynthesis of nitric oxide. The (constitutive) endothelial isoform of NOS is activated by the influx of calcium induced by shear stress or the binding of agonists to their receptors on the surfaces of endothelial cells. Endothelial NOS uses molecular oxygen and several cofactors to convert the amino acid L-arginine to NO, forming L-citrulline as a by-product. The molecular chaperone HSP90 is known to facilitate this reaction. Abbreviations for Figs 17.1 and 17.2 (see text for cofactor abbreviations): Ach, acetylcholine; ADP, adenosine diphosphate; AVP, arginine vasopressin; BK, bradykinin; cGMP, cyclic-3'5'-guanosine monophosphate; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; GC, guanylate cyclase; GTP, guanosine triphosphate; HSP90, heat shock protein 90; L-arg, L-arginine; MLC, myosin light-chains; NO, nitric oxide; PKG, protein kinase G; SP, substance P.

1980 that evidence for an endothelium-derived substance required for relaxation of blood vessels first emerged [3]. Seven years later, Palmer and colleagues and Ignarro and colleagues independently proposed that this substance, initially referred to as Endothelium-Derived Relaxing Factor (EDRF), was in fact NO - a short-lived, highly diffusible molecule whose biosynthesis, rapid diffusion and stimulation of guanylate cyclase are now known to underlie a spectrum of physiological responses in the body [4,5]. In the cerebrovascular system, NO can be synthesized by endothelial cells, smooth muscle cells and adventitial neurons (nervi vasorum), although activated macrophages, neutrophils, astrocytes and adventitial fibroblasts may also participate in NO biosynthesis under certain conditions (Fig. 17.3). It is important to note that oxyhemoglobin and oxygen-derived free radicals (both implicated in the pathogenesis of post-subarachnoid hemorrhage cerebral vasospasm) can chemically react with NO to inactivate it, while nitrovasodilators, such as glyceryl trinitrate, sodium nitroprusside and amyl nitrite, are "nitrergic" in that they result in the release of NO, either directly or indirectly [1].

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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