title: Attenuation of angiotensin type 2 receptor function in the rostral ventrolateral medullary pressor area of the spontaneously hypertensive rat.
abstract: We hypothesized that blockade of angiotensin II type 2 receptors (AT2Rs) in the rostral ventrolateral medullary pressor area (RVLM) may elicit sympathoexcitatory responses which are smaller in hypertensive rats compared to normotensive rats. This hypothesis was tested in urethane-anesthetized, artificially ventilated male 14-week-old spontaneously hypertensive rats (SHR). Age-matched male Wistar-Kyoto rats (WKY) and Wistar rats were used as controls. PD123319 (AT2R antagonist) was microinjected into the RVLM and mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) were recorded. Increases in MAP, HR and GSNA elicited by unilateral microinjections of PD123319 into the RVLM were significantly smaller in SHR when compared with those in WKY and Wistar rats. Unilateral microinjections of l-glutamate (l-Glu) into the RVLM elicited greater increases in MAP and GSNA in SHR compared to those in WKY. AT2R immunoreactivity was demonstrated in the RVLM neurons which were retrogradely labeled from the intermediolateral cell column (IML) of the spinal cord. These results indicate that AT2Rs are present on the RVLM neurons projecting to the IML and their blockade results in sympathoexcitatory responses. Activation of AT2Rs has an inhibitory influence in the RVLM and these receptors are tonically active. Attenuation of the function of AT2Rs in the RVLM may play a role in genesis and/or maintenance of hypertension in SHR.
authors.affiliation: a Department of Neurological Surgery , Rutgers New Jersey Medical School , Newark , NJ , USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawabe
authors.affiliation: a Department of Neurological Surgery , Rutgers New Jersey Medical School , Newark , NJ , USA.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iwasa
authors.affiliation: a Department of Neurological Surgery , Rutgers New Jersey Medical School , Newark , NJ , USA.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kawabe
authors.affiliation: a Department of Neurological Surgery , Rutgers New Jersey Medical School , Newark , NJ , USA.
authors.forename: Hreday N
authors.initials: HN
authors.lastname: Sapru
mesh_terms: D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D008845:Microinjections; D009474:Neurons / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D066152:Spinal Cord Lateral Horn / Q000378:metabolism; D013153:Splanchnic Nerves / Q000187:drug effects*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319; D018698:Glutamic Acid
keywords: Blood pressure; PD123319; hypertension; microinjections; sympathetic nerve activity
references.citation: J Comp Neurol. 1999 May 3;407(2):193-206
references.pmid: 10213091
references.citation: Hypertension. 2000 Jan;35(1 Pt 2):155-63
references.pmid: 10642292
references.citation: Braz J Med Biol Res. 2000 Jun;33(6):643-52
references.pmid: 10829092
references.citation: Physiol Genomics. 2000 Apr 27;2(3):137-42
references.pmid: 11015592
references.citation: News Physiol Sci. 1999 Aug;14:155-161
references.pmid: 11390842
references.citation: J Appl Physiol (1985). 2002 May;92(5):2153-61
references.pmid: 11960969
references.citation: Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):467-72
references.pmid: 12010194
references.citation: Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):491-6
references.pmid: 12010197
references.citation: Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):514-21
references.pmid: 12010201
references.citation: J Hypertens. 2002 Sep;20(9):1675-88
references.pmid: 12195099
references.citation: Braz J Med Biol Res. 2002 Sep;35(9):1047-59
references.pmid: 12219176
references.citation: Hypertension. 2002 Oct;40(4):552-9
references.pmid: 12364362
references.citation: Hypertension. 2002 Oct;40(4):560-5
references.pmid: 12364363
references.citation: Acta Physiol Scand. 2003 Mar;177(3):209-18
references.pmid: 12608991
references.citation: Blood Press. 2003;12(2):70-88
references.pmid: 12797627
references.citation: Br J Pharmacol. 2003 Nov;140(5):987-95
references.pmid: 14530222
references.citation: Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2289-97
references.pmid: 15615839
references.citation: Acta Physiol Scand. 1979 Jun;106(2):169-76
references.pmid: 159600
references.citation: Hypertension. 2005 Aug;46(2):349-54
references.pmid: 15998710
references.citation: Brain Res. 2005 Oct 5;1058(1-2):161-6
references.pmid: 16143317
references.citation: Nat Rev Neurosci. 2006 May;7(5):335-46
references.pmid: 16760914
references.citation: Brain Res. 2006 Aug 2;1102(1):117-26
references.pmid: 16797500
references.citation: Hypertension. 2008 Feb;51(2):521-7
references.pmid: 18086951
references.citation: Neuroscience. 2008 May 15;153(3):605-17
references.pmid: 18424005
references.citation: Curr Hypertens Rep. 2008 Jun;10(3):188-93
references.pmid: 18765088
references.citation: Hypertension. 2008 Oct;52(4):708-14
references.pmid: 18768398
references.citation: Hypertens Res. 2008 Jul;31(7):1445-54
references.pmid: 18957816
references.citation: Brain Res. 2009 Jan 12;1248:115-26
references.pmid: 19022229
references.citation: J Med Chem. 1991 Nov;34(11):3248-60
references.pmid: 1956044
references.citation: Curr Opin Pharmacol. 2011 Apr;11(2):124-30
references.pmid: 21159555
references.citation: Int J Hypertens. 2012;2012:351758
references.pmid: 23320146
references.citation: Hypertension. 2013 Aug;62(2):281-7
references.pmid: 23774228
references.citation: PLoS One. 2013 Aug 14;8(8):e70976
references.pmid: 23967142
references.citation: Am J Physiol Heart Circ Physiol. 2014 Feb;306(3):H438-49
references.pmid: 24285114
references.citation: Brain Res. 1989 Mar 13;482(1):12-22
references.pmid: 2565136
references.citation: J Renin Angiotensin Aldosterone Syst. 2001 Mar;2(1_suppl):S120-S124
references.pmid: 28095229
references.citation: Am J Physiol. 1979 Jan;236(1):H174-82
references.pmid: 434168
references.citation: Neuropharmacology. 1983 Sep;22(9):1071-9
references.pmid: 6138727
references.citation: Hypertension. 1982 May-Jun;4(3 Pt 2):208-25
references.pmid: 7040239
references.citation: Am J Physiol. 1995 Jan;268(1 Pt 1):C278-82
references.pmid: 7840157
references.citation: J Clin Invest. 1995 Feb;95(2):651-7
references.pmid: 7860748
references.citation: Am J Physiol. 1993 Sep;265(3 Pt 1):C607-16
references.pmid: 8214016
references.citation: J Comp Neurol. 1996 Sep 23;373(3):322-39
references.pmid: 8889931
references.citation: Clin Exp Pharmacol Physiol. 1997 Jan;24(1):83-90
references.pmid: 9043811
references.citation: Endocrinology. 1997 May;138(5):2195-8
references.pmid: 9112419
references.citation: Brain Res. 1997 Oct 24;772(1-2):107-14
references.pmid: 9406962
references.citation: Brain Res Bull. 1998;45(2):189-97
references.pmid: 9443839
references.citation: Brain Res Bull. 1998 Sep 1;47(1):17-28
references.pmid: 9766385