Prostaglandin H synthase and vascular function

Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in the production of prostaglandins and thromboxane, which are important regulators of vascu lar function. Under normal physiological conditions, PGHS-dependent vasodil ators (such as prostacyclin) modulate vascular tone. However, PGHS-dependen t vasoconstriction (mediated by thromboxane and/or its immediate precursor, PGH,) predominates in some vascular pathologies (eg, systemic hypertension , diabetes, cerebral ischemia, and aging). This review will discuss the rol e of PGHS-dependent modulation of vascular function in a number of vascular beds (systemic, pulmonary, cerebral, and uterine) with an emphasis on vasc ular pathophysiology. Moreover, the specific contributions of the different isoforms (PGHS-1 and PGHS-2) are discussed. Understanding the role of PGHS in vascular function is of particular importance because they are the targ ets of the commonly used nonsteroidal antiinflammatory drugs (NSAIDs), whic h include aspirin and ibuprofen. Importantly, with the advent of specific P GHS-2 inhibitors for treatment of conditions such as chronic inflammatory d isease, it is an opportune time to review the data regarding PGHS-dependent modulation of vascular function.