{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:45:15Z","timestamp":1790459115674,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Small GTPase Ras-related protein 1 (Rap1b) controls several basic cellular phenomena, and its deletion in mice leads to several cardiovascular defects, including impaired adhesion of blood cells and defective angiogenesis. We found that\n              <jats:italic>Rap1b<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice develop cardiac hypertrophy and hypertension. Therefore, we examined the function of Rap1b in regulation of blood pressure.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              <jats:italic>Rap1b<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice developed cardiac hypertrophy and elevated blood pressure, but maintained a normal heart rate. Correcting elevated blood pressure with losartan, an angiotensin II type 1 receptor antagonist, alleviated cardiac hypertrophy in\n              <jats:italic>Rap1b<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, suggesting a possibility that cardiac hypertrophy develops secondary to hypertension. The indices of renal function and plasma renin activity were normal in\n              <jats:italic>Rap1b<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Ex vivo, we examined whether the effect of Rap1b deletion on smooth muscle\u2013mediated vessel contraction and endothelium-dependent vessel dilation, 2 major mechanisms controlling basal vascular tone, was the basis for the hypertension. We found increased contractility on stimulation with a thromboxane analog or angiotensin II or phenylephrine along with increased inhibitory phosphorylation of myosin phosphatase under basal conditions consistent with elevated basal tone and the observed hypertension. Cyclic adenosine monophosphate\u2013dependent relaxation in response to Rap1 activator, Epac, was decreased in vessels from\n              <jats:italic>Rap1b<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Defective endothelial release of dilatory nitric oxide in response to elevated blood flow leads to hypertension. We found that nitric oxide\u2013dependent vasodilation was significantly inhibited in Rap1b-deficient vessels.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>This is the first report to indicate that Rap1b in both smooth muscle and endothelium plays a key role in maintaining blood pressure by controlling normal vascular tone.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.114.303678","type":"journal-article","created":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T02:55:19Z","timestamp":1398999319000},"page":"1486-1494","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Rap1b in Smooth Muscle and Endothelium Is Required for Maintenance of Vascular Tone and Normal Blood Pressure"],"prefix":"10.1161","volume":"34","author":[{"given":"Sribalaji","family":"Lakshmikanthan","sequence":"first","affiliation":[{"name":"From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz J.","family":"Zieba","sequence":"additional","affiliation":[{"name":"From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Dong","family":"Ge","sequence":"additional","affiliation":[{"name":"From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Momotani","sequence":"additional","affiliation":[{"name":"From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zheng","sequence":"additional","affiliation":[{"name":"From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Lund","sequence":"additional","affiliation":[{"name":"From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykhaylo V.","family":"Artamonov","sequence":"additional","affiliation":[{"name":"From the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); 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