Localization of cyclooxygenase isozymes in cardiovascular tissues of dogs treated with naproxen.
Prostaglandins have diverse roles in the cardiovascular system mediating both physiologic and inflammatory responses. Two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, catalyze prostaglandin production. In many tissues and cell types studied, cyclooxygenase-1 is constitutively active whereas cyclooxygenase-2 expression is primarily responsible for prostaglandin production during inflammation. However, little information exists concerning which isoform is responsible for prostaglandin-mediated effects in the heart. We examined cyclooxygenase-1 and cyclooxygenase-2 expression in heart and vascular tissue of dogs using isoform-specific antibodies. In addition, tissues from dogs treated with naproxen (5-10mg/kg/day), an inhibitor of prostaglandin production were also examined. Cyclooxygenase-1 expression was evident in endothelial cells of the microvasculature of the heart, aorta and renal artery. Cyclooxygenase-1 expression was also found in fibrocytes of the tricuspid valve and in the chordae tendinae. Animals treated with naproxen exhibited a similar pattern and intensity of cyclooxygenase-1 staining. No cyclooxygenase-2 expression was evident in cardiac tissue. However, minimal cyclooxygenase-2 immunoreactivity was present in the vascular endothelial cells of small myocardial blood vessels located in several regions of the heart as well as in endothelial cells of the aorta. These data may expand our understanding of the effects of non-steroidal anti-inflammatory drugs on cardiac function.
Stanfield
K M
KM
Metabolism and Safety Evaluation, Safety Pharmacology Department, Global Toxicology, Pharmacia Corporation, 4901 Searle Parkway, Skokie, IL 60077, USA.
Khan
K N
KN
Gralinski
M R
MR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002319:Cardiovascular System / Q000187:drug effects* / Q000201:enzymology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D005260:Female; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009288:Naproxen / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D009288:Naproxen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases