title: The neurogenic phase of angiotensin II-salt hypertension is prevented by chronic intracerebroventricular administration of benzamil.
abstract: Hypertension induced by chronic administration of angiotensin II (AngII) is exacerbated by high-salt intake. Previous studies have demonstrated that this salt-sensitive component is due to increased activity of the sympathetic nervous system, suggesting an interaction of plasma AngII with sodium-sensitive regions of the brain. This study tested the hypothesis that the salt-sensitive component of AngII-induced hypertension would be prevented by intracerebroventricular (ICV) administration of the sodium channel/transporter blocker benzamil. Male Sprague Dawley rats were instrumented to measure mean arterial pressure (MAP) by radio telemetry and for ICV administration of benzamil or vehicle and placed in metabolic cages for measurement of sodium and water intake and excretion. In rats consuming a high-salt diet (2.0% NaCl) and treated with ICV vehicle, administration of AngII (150 ng/kg/min, sc) for 13 days increased MAP by ~30 mmHg. ICV administration of benzamil (16 nmol/day) had no effect during the first 5 days of AngII, but returned MAP to control levels by Day 13. There were minimal or no differences between ICV vehicle or benzamil groups in regards to sodium and water balance. A lower dose of ICV benzamil administered ICV at 8 nmol/day had no effect on the MAP response to AngII in rats on a high-salt diet. Finally, in contrast to rats on a high-salt diet, AngII had negligible effects on MAP in rats consuming a low-salt diet (0.1% NaCl) and there were no differences in any variable between ICV benzamil (16 nmol/day) and ICV vehicle-treated groups. We conclude that the salt-sensitive component of AngII-induced hypertension is dependent on benzamil blockable sodium channels or transporters in the brain.
authors.affiliation: Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: John W
authors.initials: JW
authors.lastname: Osborn
authors.affiliation: Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Dalay M
authors.initials: DM
authors.lastname: Olson
authors.affiliation: Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Pilar
authors.initials: P
authors.lastname: Guzman
authors.affiliation: Department of Physiology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Toney
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Fink
keywords: Neurogenic hypertension; salt‐dependent hypertension; sympathetic nerve activity
references.citation: Curr Hypertens Rep. 2011 Jun;13(3):221-8
references.pmid: 21298369
references.citation: Physiol Rep. 2013 Oct;1(5):e00128
references.pmid: 24303192
references.citation: Am J Physiol. 1998 Mar;274(3):R635-44
references.pmid: 9530228
references.citation: Hypertension. 1995 Oct;26(4):649-55
references.pmid: 7558226
references.citation: J Physiol. 2010 Sep 15;588(Pt 18):3375-84
references.pmid: 20603334
references.citation: Hypertension. 2002 Jul;40(1):96-100
references.pmid: 12105145
references.citation: Exp Physiol. 2012 Jan;97(1):80-8
references.pmid: 21967900
references.citation: Hypertension. 2002 Feb;39(2 Pt 2):557-61
references.pmid: 11882607
references.citation: Curr Opin Cardiol. 2006 Jul;21(4):295-304
references.pmid: 16755197
references.citation: Hypertension. 2007 Sep;50(3):547-56
references.pmid: 17646575
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1787-97
references.pmid: 16141309
references.citation: Invest Radiol. 1988 Jul;23(7):534-6
references.pmid: 3170143
references.citation: Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1519-29
references.pmid: 15937098
references.citation: Exp Physiol. 2010 Jan;95(1):61-8
references.pmid: 19717492
references.citation: J Am Soc Nephrol. 2002 May;13(5):1131-5
references.pmid: 11960999
references.citation: Pflugers Arch. 2007 Apr;454(1):1-18
references.pmid: 17120021
references.citation: Am J Physiol. 1999 Jun;276(6):H2215-20
references.pmid: 10362706
references.citation: Clin Exp Pharmacol Physiol. 2008 May;35(5-6):687-94
references.pmid: 18387084
references.citation: Circ Res. 1976 Dec;39(6):788-97
references.pmid: 1000772
references.citation: Brain Res. 1973 Mar 30;52:323-32
references.pmid: 4739806
references.citation: J Am Soc Nephrol. 2008 Oct;19(10):1845-54
references.pmid: 18753254
references.citation: Am J Physiol. 1995 Sep;269(3 Pt 2):H1044-7
references.pmid: 7573500
references.citation: Am J Physiol Heart Circ Physiol. 2012 Feb 1;302(3):H763-9
references.pmid: 22114134
references.citation: Hypertension. 2008 May;51(5):1265-71
references.pmid: 18378856
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Jul;299(1):R222-33
references.pmid: 20427723
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Apr;294(4):R1262-7
references.pmid: 18256139
references.citation: J Physiol. 2006 Oct 15;576(Pt 2):569-83
references.pmid: 16873404
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Dec;299(6):R1500-10
references.pmid: 20926762
references.citation: Hypertension. 2010 Mar;55(3):644-51
references.pmid: 20100996
references.citation: J Assoc Physicians India. 2004 Jan;52:53-62
references.pmid: 15633721
references.citation: Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1844-9
references.pmid: 9620916
references.citation: Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R460-9
references.pmid: 21123759
references.citation: Hypertension. 2006 Nov;48(5):927-33
references.pmid: 17000931