Differentiation of cyclooxygenase 1- and 2-derived prostanoids in mouse kidney and aorta.
Accumulating evidence indicates cyclooxygenase (COX) 1 and COX2 differentially regulate cardiovascular and renal function. We have demonstrated previously in mice that COX2 inhibition enhances angiotensin II-induced hypertension, and COX1 inhibition attenuates the pressor effect of angiotensin II. To further elucidate the mechanism underlying the functional difference of COX1 versus COX2 inhibition, the present studies examined the prostaglandin (PG) profiles derived in COX1- or COX2-inhibited mouse kidney and aorta using gas chromatographic/mass spectrometric assays. PGE2 is the most abundant prostanoid in both renal cortex and medulla in normal C57BL/6J mice, followed by PGI2, PGF2alpha and thromboxane A2. In contrast PGI2 was most abundant in aorta followed by thromboxane A2, PGE2, and PGF2alpha. PGD2 was undetectable in control kidney or aorta. At baseline, inhibition of COX1 decreased total prostaglandins in renal cortex, medulla, and aorta, whereas COX2 inhibition decreased total prostaglandins only in renal medulla. Angiotensin II infusion significantly increased COX2-dependent/COX1-independent PGE2 and PGI2 in renal cortex and medulla. Angiotensin II also significantly increased renal PGF2alpha in cortex, but not in medulla, through both COX1- and COX2-dependent mechanisms. These studies demonstrate that although COX1 primarily contributes to basal prostanoid production in the kidney and aorta, angiotensin II increases renal vasodilator prostanoids predominately via COX2 activity. These effects may contribute to the specific effect of COX2 inhibitors to increase blood pressure.
Qi
Zhonghua
Z
Division of Nephrology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA. zhonghua.qi@vanderbilt.edu
Cai
Hui
H
Morrow
Jason D
JD
Breyer
Matthew D
MD
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011453:Prostaglandins / Q000096:biosynthesis* / Q000145:classification*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2