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VOL. 74 (4) PROSTANOIDS ACTIONS IN CARDIOVASCULAR...

Palabras clave: Prostaglandinas.- Tromboxanos.- Ciclooxigenasas.-
Receptores de prostanoides.- AINEs.- Fisiopatología cardiovascular.

INTRODUCTION

Prostanoids, including prostaglandins (PGs) and thromboxanes
(TXs) are a group of bioactive lipids that play a very important role in
many physiological and pathological processes, including inflammation
(1), cancer (2), angiogenesis (3) and cardiovascular diseases (4-7).
Arachidonic acid liberated from membrane phospholipids by several
phospholipases, is metabolized by the sequential action of
cyclooxygenases (COX) and prostaglandin or thromboxane synthases to
produce the diverse classes of prostanoids (8, 9). COX enzymes catalyze
the formation of an unstable endoperoxide intermediate, PGH2, which in
turn can be metabolized by cell-specific isomerases and synthases to a
range of eicosanoids with potent and diverse biological effects, as PGD2,
PGE2, PGF2a, PGI2, and TXA2 (Figure 1). Finally after their synthesis,
prostanoids are quickly released to the extracellular medium exerting
multiple effects upon interaction with prostanoid receptors present in the
neighbouring cells.

CYCLOOXYGENASES

There are two main COX isoenzymes named COX-1 and COX-2,
encoded by two separate genes (8-10). A COX-3 enzyme derived from
alternative splicing of the COX-1 gene has been also described, although
its role is still unclear (11). COX-1 is constitutively expressed in most,
but not all, cell types and tissues and is responsible for vascular, renal and
gastric homeostasis (12). In contrast, COX-2 expression is generally
induced at sites of inflammation by many stimuli that includes among
others, proinflammatory cytokines as interleukin (IL)-1ß, tumor necrosis
factor (TNF)-a, growth factors, mechanical stress, oxidized lipids, free
radicals and bacterial products (9-13). Those stimuli activate many

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