title: Caveolae are essential for angiotensin II type 1 receptor-mediated ANP secretion.
abstract: Caveolae may act as mechanosensors and function as binding sites for calcium ions. The intracaveolar localization of atrial natriuretic peptide (ANP) derived from the direct interaction of atrial granules with caveolae has been demonstrated. The aim of this study was to define the effect of caveolae on ANP secretion induced by stretch and angiotensin II. The isolated perfused beating atria from Sprague-Dawley rats were used. To disrupt caveolae, 10mM methyl-β-cyclodextrin (MbCD) was applied for 1h and the number of caveoli were markedly decreased. MbCD increased basal ANP secretion and atrial diastolic pressure. The molecular profile of ANP in perfusate from control atria showed mainly one major peak corresponded to synthetic ANP whereas that from MbCD-treated atria showed two major immunoreactive peaks corresponded to synthetic rat ANP and proANP. High atrial stretch induced by elevating the height of outflow catheter from 5 cm H₂O to 7.5 cm H₂O increased atrial contractility and ANP secretion. The response of ANP secretion to high stretch was attenuated in MbCD-pretreated atria. Pretreatment with MbCD abolished angiotensin II-induced suppression and losartan-induced stimulation of ANP secretion. However, the effect of angiotenisin (1-7) on ANP secretion was not altered by MbCD treatment. The expression of angiotensin II type 1 receptor protein was reduced by MbCD treatment. These data suggest that caveolae are essential for angiotensin II type 1 receptor-mediated ANP secretion and relate to the processing of proANP.
authors.affiliation: Department of Physiology, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Young-Bin
authors.initials: YB
authors.lastname: Oh
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lim
authors.forename: Hyung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D001794:Blood Pressure; D002404:Catheterization; D021941:Caveolae / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D007260:Infusion Pumps; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques; D010477:Perfusion; D011498:Protein Precursors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D011498:Protein Precursors; D044140:Receptor, Angiotensin, Type 1; C472610:atrial natriuretic peptide, rat; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D019808:Losartan