Excess dietary salt alters angiotensinergic regulation of neurons in the rostral ventrolateral medulla.
Excess dietary salt intake contributes to or exacerbates some forms of hypertension by increasing sympathetic nerve activity (SNA) and arterial blood pressure (ABP) through angiotensin II (Ang II) type 1 receptor activation in the rostral ventrolateral medulla (RVLM). Despite this interaction among dietary salt, Ang II, and the RVLM, no studies have directly examined whether dietary salt by itself alters Ang II-dependent responses and regulation of RVLM neurons, SNA, and ABP. Therefore, the present study directly tested this hypothesis. Male Sprague-Dawley rats were fed normal chow and given access to water or 0.9% NaCl solution for 14 days. Unilateral injection of Ang II (0.6, 6, and 60 pmol) into the RVLM produced a significantly greater increase in renal SNA and mean ABP of rats drinking 0.9% NaCl versus water. However, dietary salt did not alter mRNA levels of RVLM Ang II type 1a receptors or the SNA and ABP responses to stimulation of the dorsolateral funinculus. Additional experiments demonstrate that blockade of RVLM Ang II type 1 receptors significantly reduced renal SNA, splanchnic SNA, and mean ABP of rats drinking 0.9% NaCl but not water. Blockade of iontotropic glutamate receptors had no effect. Altogether, these findings suggest that elevated dietary salt enhances the sympathoexcitatory actions of Ang II in the RVLM via changes in the intrinsic properties of RVLM neurons. Moreover, elevated dietary salt intake differentially affects the tonic activity of the peripheral versus brain RVLM Ang II type 1 receptors to regulate baseline SNA and ABP.
Adams
Julye M
JM
Department of Physiology, University of Kentucky, Lexington, KY 40536-0298, USA.
McCarthy
John J
JJ
Stocker
Sean D
SD
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary; D007736:Kynurenic Acid; D019808:Losartan
Auton Neurosci. 2003 Sep 30;107(2):85-98
12963419
Circulation. 2002 Oct 8;106(15):1957-61
12370219
Clin Exp Pharmacol Physiol. 2008 May;35(5-6):695-700
18067592
Clin Exp Hypertens A. 1983;5(5):759-74
6883743
Nat Rev Neurosci. 2006 May;7(5):335-46
16760914
Curr Hypertens Rep. 2007 Jun;9(3):228-35
17519130
Clin Exp Hypertens A. 1984;6(9):1543-58
6509785
Brain Res Bull. 1998 Sep 1;47(1):17-28
9766385
Metabolism. 2007 Mar;56(3):373-9
17292726
Neuroendocrinology. 1985 Jan;40(1):2-24
3969196
Hypertension. 2002 Oct;40(4):552-9
12364362
Am J Physiol. 1995 Jan;268(1 Pt 2):R272-7
7840331
Am J Physiol. 1994 Oct;267(4 Pt 2):H1549-56
7943401
Acta Physiol Scand. 2003 Jan;177(1):43-55
12492778
Hypertension. 1989 Aug;14(2):177-83
2759678
Am J Physiol Heart Circ Physiol. 2003 Nov;285(5):H1949-55
12842816
Am J Physiol. 1996 Aug;271(2 Pt 2):R361-7
8770135
Exp Neurol. 2004 Aug;188(2):238-45
15246823
Brain Res. 1997 Mar 7;750(1-2):305-10
9098557
Hypertension. 1999 Dec;34(6):1301-7
10601134
Hypertension. 1996 Mar;27(3 Pt 2):598-606
8613210
Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1675-82
17185407
Hypertension. 1993 Dec;22(6):929-33
7902336
J Comp Neurol. 1992 Feb 22;316(4):467-84
1577995
Hypertension. 2007 Aug;50(2):354-9
17592069
Curr Hypertens Rep. 2007 Jun;9(3):222-7
17519129
Clin Exp Pharmacol Physiol. 2005 May-Jun;32(5-6):426-32
15854153
Hypertension. 2006 Jun;47(6):1054-61
16618838
Hypertension. 2005 Jan;45(1):98-102
15557392
Hypertension. 2003 Mar;41(3 Pt 2):744-50
12623990
Hypertension. 1994 Jan;23(1 Suppl):I137-41
7506698
Hypertension. 2003 May;41(5):1168-73
12654708
Circ Res. 1996 Feb;78(2):274-82
8575071
Hypertension. 1990 Aug;16(2):121-30
2379945
Am J Physiol. 1999 Jun;276(6):R1600-7
10362737