{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:18:50Z","timestamp":1783721930607,"version":"3.55.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Endothelium-derived nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in modulating vascular tone in a distinct vessel size\u2013dependent manner; NO plays a dominant role in conduit arteries and EDH in resistance vessels. We have recently demonstrated that endothelial NO synthase (eNOS) is functionally suppressed in resistance vessels through caveolin-1 (Cav-1)-dependent mechanism, switching its function from NO to EDH\/hydrogen peroxide generation in mice. Here, we examined the possible importance of the physiological balance between NO and EDH in cardiovascular homeostasis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>We used 2 genotypes of mice in which eNOS activity is genetically upregulated; Cav-1-knockout (Cav-1-KO) and endothelium-specific eNOS transgenic (eNOS-Tg) mice. Isometric tension recordings and Langendorff experiments with isolated perfused hearts showed that NO-mediated relaxations were significantly enhanced, whereas EDH-mediated relaxations were markedly reduced in microcirculations. Importantly, impaired EDH-mediated relaxations of small mesenteric arteries from Cav-1-KO mice were completely rescued by crossing the mice with those with endothelium-specific overexpression of Cav-1. Furthermore, both genotypes showed altered cardiovascular phenotypes, including cardiac hypertrophy in Cav-1-KO mice and hypotension in eNOS-Tg mice. Finally, we examined cardiac responses to chronic pressure overload by transverse aortic constriction in vivo. When compared with wild-type mice, both Cav-1-KO and eNOS-Tg mice exhibited reduced survival after transverse aortic constriction associated with accelerated left ventricular systolic dysfunction, reduced coronary flow reserve, and enhanced myocardial hypoxia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>These results indicate that excessive endothelium-derived NO with reduced EDH impairs cardiovascular homeostasis in mice in vivo.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.306499","type":"journal-article","created":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T04:09:41Z","timestamp":1446782981000},"page":"97-107","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Disruption of Physiological Balance Between Nitric Oxide and Endothelium-Dependent Hyperpolarization Impairs Cardiovascular Homeostasis in Mice"],"prefix":"10.1161","volume":"36","author":[{"given":"Shigeo","family":"Godo","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayuko","family":"Sawada","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Saito","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Ikeda","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Budbazar","family":"Enkhjargal","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Suzuki","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Tanaka","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Shimokawa","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-08-1169"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20090096"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0790-8"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2011.585658"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu427"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb10306.x"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb11752.x"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.3.415"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/46816"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2003.11.014"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/24388"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4805"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10506"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.237636"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199611000-00014"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119826"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2603"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.270215"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000050145.25589.65"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.05.039"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080106"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144318"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-12-0197"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.71.301"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105408200"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4394"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004146"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05602"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-08-0481"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.731679"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.12.3341"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.2.H459"},{"key":"e_1_3_5_34_2","first-page":"H865","article-title":"cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries.","volume":"268","author":"Olmos L","year":"1995","unstructured":"Olmos L, Mombouli JV, Illiano S, Vanhoutte PM. cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries. Am J Physiol. 1995;268(2 pt 2):H865\u2013H870.","journal-title":"Am J Physiol"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706363"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19351"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.198754"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.240242"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00380.2002"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062340"},{"key":"e_1_3_5_41_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-88-470-5367-0_2","volume-title":"In: Coronary Microvascular Dysfunction","author":"Crea F","year":"2014","unstructured":"Crea F, Lanza G, Camici P. Mechanisms of coronary microvascular dysfunction. In: Coronary Microvascular Dysfunction. Milan, Italy: Springer; 2014:31\u201347."},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.15.1854"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-006-0626-z"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht249"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0815-3"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6278"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2005.07.007"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042934"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.012957"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp457"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-66-0053"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e31829e8807"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.115.306499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:08:28Z","timestamp":1715555308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.115.306499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1161\/ATVBAHA.115.306499"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.115.306499","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1]]},"assertion":[{"value":"2015-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}