The nitric oxide pathway in the cardiovascular system.
The present review analyzes the role nitric oxide (NO) plays in the homeostasis of the cardiovascular system. By regulating vascular smooth muscle cell and myocyte contractility, myocardial oxygen consumption and renal tubular transport, this simple molecule plays a central role in the control of vascular tone, cardiac contractility and short and long term regulation of arterial pressure. Fifteen years ago, all we knew about NO is that it had very similar properties as those of endothelium-derived relaxing factor and that its action was probably mediated by cGMP. An enormous amount of knowledge has since been amassed on the biochemical pathways that NO follows from the moment it is synthesized from L-arginine until the physiological or pathological actions take place in the effector cells. This review intends to organize this knowledge in a fashion that is easy to understand. We will dissect the NO pathway in different steps, focusing on the physiological and pathophysiological actions of the isoenzymes which synthesize NO, the molecules involved in this synthesis such as caveolins, protein kinases and cofactors, the situations in which endogenous inhibitors of NO synthase are formed from L-arginine instead of NO, the way in which NO exerts its physiological actions through cGMP-dependent protein kinases and finally, the pathological routes NO may follow when the oxidative status of the cell is high.
Llorens
S
S
Facultad de Medicina de la Universidad de Castilla La Mancha y Centro Regional de Investigaciones Biológicas, Campus de Albacete, 02071 Albacete, Spain.
Jordán
J
J
Nava
E
E
D000818:Animals; D001120:Arginine / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D030421:Peroxynitrous Acid / Q000378:metabolism
D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D001120:Arginine; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D006152:Cyclic GMP