It is widely believed that salt-dependent hypertension is induced and maintained by expansion of intravascular fluid volume resulting from excessive retention of sodium. The purpose of this brief article is to present a series of arguments in support of the thesis that volume overload per se does not raise the arterial blood pressure. Several investigators in the 1960s and 1970s reported that excessive retention of salt – regardless of cause – leads to sympathetic activation mediated by the effects of the Na ion on α2-adrenergic receptors located mostly in the brainstem. In recent years, the cloning and characterization of α2-adrenergic receptors subtypes permitted differentiation of their hemodynamic effects via use of salt loading of nephrectomized animals submitted to genetic engineering or gene treatment. These studies indicate that sodium alters the balance between the sympathoinhibitory α2A-adrenergic receptors and the sympathoexcitatory α2B-adrenergic receptors, leading to a hyperadrenergic hypertensive state unrelated to volume overload.
Hypertension and Atherosclerosis Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
Correspondence to Haralambos Gavras, MD, FRCP, Hypertension and Atherosclerosis Section, Boston University School of Medicine, W508 700 Albany Street, Boston, MA 02118, USA. Tel: +1 617 638 4025; fax: +1 617 638 4027; e-mail: email@example.com
Abbreviations: AS-ODN, antisense-oligodeoxynucleotide; BP, blood pressure; DOCA, deoxycorticosterone acetate; PRA, plasma renin activity; rAAV, recombinant adeno-associated virus; SIADH, syndrome of inappropriate antidiuretic hormone
Received 12 September, 2011
Revised 15 November, 2011
Accepted 18 November, 2011