title: The central role of the brain in salt-sensitive hypertension.
abstract: OBJECTIVE
  To integrate recent studies showing that abnormal Na transport in the central nervous system plays a pivotal role in genetic models of salt-sensitive hypertension.
  
  
  RESULTS
  Na transport-regulating mechanisms classically considered to reflect renal control of the blood pressure, i.e. aldosterone-mineralocorticoid receptors-epithelial sodium channels-Na/K-ATPase, have now been demonstrated to be present in the central nervous system contributing to regulation of cerebrospinal fluid [Na] by the choroid plexus and to neuronal responsiveness to cerebrospinal fluid/brain [Na]. Dysfunction of either or both can activate central nervous system pathways involving 'ouabain' and angiotensin type 1 receptor stimulation. The latter causes sympathetic hyperactivity and adrenal release of marinobufagenin - a digitalis-like inhibitor of the alpha1 Na/K-ATPase isoform - both contributing to hypertension on high salt intake. Conversely, specific central nervous system blockade of mineralocorticoid receptors or epithelial sodium channels prevents the development of hypertension on high salt intake, irrespective of the presence of a 'salt-sensitive kidney'. Variants in the coding regions of some of the genes involved in Na transport have been identified, but sodium sensitivity may be mainly determined by abnormal regulation of expression, pointing to primary abnormalities in regulation of transcription.
  
  
  CONCLUSIONS
  Looking beyond the kidney is providing new insights into mechanisms contributing to salt-sensitive hypertension, which will help to dissect the genetic factors involved and to discover novel strategies to prevent and treat salt-sensitive hypertension.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.forename: Md Shahrier
authors.initials: MS
authors.lastname: Amin
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D002018:Bufanolides; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism; D000075702:Nedd4 Ubiquitin Protein Ligases; D010042:Ouabain / Q000819:agonists; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists; D011945:Receptors, Angiotensin / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D051437:Renal Insufficiency / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D012084:Renin-Angiotensin System; D012982:Sodium, Dietary / Q000008:administration & dosage; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014662:Vasoconstrictor Agents; D000099291:Adducins; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002018:Bufanolides; D002148:Calmodulin-Binding Proteins; D003577:Cytochrome P-450 Enzyme System; D056827:Endosomal Sorting Complexes Required for Transport; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; D010042:Ouabain; D017346:Protein Serine-Threonine Kinases; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D018161:Receptors, Mineralocorticoid; D017483:Receptors, Vasopressin; D012982:Sodium, Dietary; D000254:Sodium-Potassium-Exchanging ATPase; D044767:Ubiquitin-Protein Ligases; D014662:Vasoconstrictor Agents; D000099291:Adducins; D000099184:Serum-Glucocorticoid Regulated Kinases; C093896:marinobufagenin; C120299:Sik1 protein, rat