PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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: Michael G Harrington; Alfred N Fonteh; Xianghong Arakaki; Robert P Cowan; Laurel E Ecke; Hailey Foster; Andreas F Hühmer; Roger G Biringer Journal: Headache Date: 2009-10-21 Impact factor: 5.887