title: Critical Role of Striatin in Blood Pressure and Vascular Responses to Dietary Sodium Intake.
abstract: Striatin is a protein regulator of vesicular trafficking in neurons that also binds caveolin-1 and Ca(2+)-calmodulin and could activate endothelial nitric oxide synthase. We have shown that striatin colocalizes with the mineralocorticoid receptor and that mineralocorticoid receptor activation increases striatin levels in vascular cells. To test whether striatin is a regulator of vascular function, wild-type and heterozygous striatin-deficient mice (Strn(+/-)) were randomized in crossover intervention to restricted (0.03%) and liberal sodium (1.6%) diets for 7 days on each diet, and blood pressure and aortic vascular function were measured. Compared with wild-type, sodium restriction significantly reduced blood pressure in Strn(+/-). On liberal salt intake, phenylephrine and high KCl caused a greater vascular contraction in Strn(+/-) than wild-type, and endothelium removal, nitric oxide synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ enhanced phenylephrine contraction to a smaller extent in Strn(+/-) than wild-type. On liberal salt, acetylcholine relaxation was less in Strn(+/-) than in wild-type, and endothelium removal, L-NAME, and ODQ blocked acetylcholine relaxation, suggesting changes in endothelial NO-cGMP. On liberal salt, endothelial nitric oxide synthase mRNA expression and the ratio of endothelial nitric oxide synthase activator pAkt/total Akt were decreased in Strn(+/-) versus wild-type. Vascular relaxation to NO donor sodium nitroprusside was not different among groups. Thus, striatin deficiency is associated with salt sensitivity of blood pressure, enhanced vasoconstriction, and decreased vascular relaxation, suggesting a critical role for striatin, through modulation of endothelial NO-cGMP, in regulation of vascular function and BP during changes in sodium intake.
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Garza
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Luminita H
authors.initials: LH
authors.lastname: Pojoga
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Burhanuddin
authors.initials: B
authors.lastname: Moize
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Wan M
authors.initials: WM
authors.lastname: Hafiz
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Opsasnick
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Waleed T
authors.initials: WT
authors.lastname: Siddiqui
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Michael
authors.initials: M
authors.lastname: Horenstein
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
authors.affiliation: From the Cardiovascular Endocrine Section, Division of Endocrinology, Diabetes and Hypertension (A.E.G., L.H.P., B.M., W.M.H., G.K.A., G.H.W.), and Division of Vascular Surgery (L.A.O., W.T.S., M.H., R.A.K.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. raouf_khalil@hms.harvard.edu.
authors.forename: Raouf A
authors.initials: RA
authors.lastname: Khalil
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012982:Sodium, Dietary; C491924:Strn protein, mouse; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester
keywords: blood pressure; contraction; endothelium; nitric oxide; smooth muscle; striatin