title: Regulation of ANP secretion from isolated atria by prostaglandins and cyclooxygenase-2.
abstract: Cyclooxygenase (COX) is a key enzyme regulating the production of various prostaglandins (PGs) from arachidonic acid. Angiotensin II has been reported to be an important inflammatory mediator, which increases COX-2. The aim of this study was to determine the role of various PGs and COX-2 in the regulation of atrial natriuretic peptide (ANP) secretion. PGF2alpha and PGD2 caused dose-dependent increases in ANP release and intra-atrial pressure. The potency for the stimulation of ANP secretion by PGF2alpha was higher than that by PGD2. In contrast, PGE2, PGI2, PGJ2, and thromboxane A2 did not show any significant effects. The increases in intra-atrial pressure and ANP secretion induced by PGF2alpha and PGD2 were significantly attenuated by the pretreatment with an inhibitor of PGF2alpha receptor. By the pretreatment with an inhibitor for phospholipase C (PLC), inositol 3-phosphate (IP3) receptor, protein kinase C (PKC), or myosin light chain kinase (MLCK), PGF2alpha-mediated increase in ANP secretion and positive inotropy were attenuated. Inhibitor for COX-1 or COX-2 did not cause any significant effects on atrial parameters. In hypertrophied rat atria, PGF2alpha-induced positive inotropy and ANP secretion were markedly attenuated whereas COX-2 inhibitor stimulated ANP secretion. The expression of COX-2 increased and the expression of PGF2alpha receptor mRNA decreased in hypertrophied rat atria. These results suggest that PGF2alpha increased the ANP secretion and positive inotropy through PLC-IP3-PKC-MLCK pathway, and the modulation of ANP secretion by COX-2 inhibitor and PGF2alpha may partly relate to the development of renal hypertension.
authors.affiliation: Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, 2-20 Keum-Am-Dong-San, Jeonju, Republic of Korea.
authors.forename: Guanyi
authors.initials: G
authors.lastname: Bai
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Amin
authors.initials: A
authors.lastname: Shah
authors.forename: Kuichang
authors.initials: K
authors.lastname: Yuan
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D016275:Atrial Function / Q000187:drug effects / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D010477:Perfusion; D015230:Prostaglandin D2 / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000235:genetics; D012077:Renal Artery / Q000601:surgery; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D044004:Xanthones / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D011453:Prostaglandins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D044004:Xanthones; C034671:prostaglandin F2alpha receptor; C121227:AL 8810; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D009320:Atrial Natriuretic Factor; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor