Regional differentiation in the rat aorta: effects of cyclooxygenase inhibitors.
Rat aortic endothelium is differentiated regionally for signaling the underlying smooth muscle via nitric oxide to increase the level of guanosine 3',5'-cyclic monophosphate (cGMP) [R.E. Abbott and D. Schachter. Am. J. Physiol. 266 (Heart Circ. Physiol. 35): H2287-H2295, 1994]. Maximal activity is just distal to the aortic arch, i.e., in the "windkessel" region, and diminishes peripherally. This report describes the same pattern of endothelial differentiation for a second signal arising from the cyclooxygenase arm of the eicosanoid pathway. Treatment of sequential segments of rat aorta in vitro with indomethacin (50 microM) or acetylsalicylate (100 microM) increased the cGMP content selectively in aortic segments prepared from the windkessel region. The indomethacin effect was eliminated by denuding the endothelium or by inhibiting cyclic nucleotide phosphodiesterase activity. Prostaglandin H2 was identified as a cyclooxygenase product involved in this signal pathway because treatment with the compound decreased cGMP levels, and this effect was eliminated by inhibiting cyclic nucleotide phosphodiesterase activity. Endothelial regulation of smooth muscle cGMP via nitric oxide and cyclooxygenase pathways supports the concept of dynamic regulation of aortic wall properties in the windkessel region.
Schachter
D
D
Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Sang
J C
JC
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016861:Cyclooxygenase Inhibitors; D011463:Prostaglandins H; D009569:Nitric Oxide; D044262:Prostaglandin H2; D006152:Cyclic GMP; D001241:Aspirin; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin