Coronary Vasomotor Responses: Role of Endothelium and Nitrovasodilators

  • E. Bassenge

Summary

The endogenous nitrovasodilator endothelium-derived nitric oxide (EDNO) is continuously synthetized enzymatically by NO synthase from L-arginine and is released from endothelial cells. Enhanced, superimposed EDNO release can be stimulated by various local and circulating factors, such as bradykinin, ATP, etc., but also most importantly by viscous drag-induced shear stress of the blood-stream acting on the endothelial lining. Thus luminal release suppresses leukocyte adhesion (expression of adhesion molecules), platelet activation, platelet adhesion, and platelet aggregation, and abluminal release counteracts myogenic and neurogenic coronary constrictor tone, thereby increasing myocardial perfusion and dilating large coronary artery calibers. Thus endothelial impairment and denudation (hypercholesterolemia, atheromatosis, balloon catheter interventions) favor excessive constrictor tone and myocardial ischemia. Under these conditions EDNO can be supplemented by compounds (e.g., nitroglycerin, isosorbide dinitrate) converted by biological systems into NO. In addition, it can be supplemented by compounds that even spontaneously release NO (e.g., sydnonimines such as SIN-1 and sodium nitroprusside). EDNO and exogenously supplemented NO stimulate soluble guanylyl cyclase, increase cGMP levels, and bring about vascular relaxation, particularly in those still compliant sections in which EDNO production is impaired and cGMP levels are thus diminished. Exogenous nitrovasodilators are preferentially converted (in the presence of cysteine) enzymatically in large coronary arteries, improving coronary conductance, and in the venous bed (preload reduction), resulting in an improved O2 supply/demand ratio. During chronic, continuous application, neurohormonal counterregulation and diminished enzymatic biotransformation into NO may reduce their effectiveness, resulting in tolerance, particularly in the most sensitive vascular sections, such as veins and coronary arteries. This drawback can be overcome by spontaneously applying NO-releasing compounds, intermittent therapy, or intermittent interposition of other vasodilator principles.

KeyWords

endothelium derived NO nitrovasodilators nitrate tolerance receptor dependent and independent NO release nitric oxide 

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© Kluwer Academic Publishers 1997

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  • E. Bassenge

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