Among these, the simultaneous inhibition of cyclooxygenase 1 (COX-1) would explain the unwanted side effects in the gastrointestinal tract and many adverse cardiovascular effects, such as high blood pressure, myocardial infarction and thrombosis.
However, the inhibition of COX-1 in cells of the gastrointestinal (GI) system and COX-2 in vascular cells translates into increased risk of serious GI adverse events and atherothrombosis and hypertension, respectively.
Pulmonary and cardiorenal cyclooxygenase-1 (COX-1), -2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) and -2 (mPGES-2) expression in a hypertension model.
In preclinical studies, we have shown that increased expression of the gene encoding the constitutive form of the cyclooxygenase gene (COX-1) results in increased production of prostacyclin and PGE2 by the lungs and inhibits endotoxin induced pulmonary hypertension and edema.