title: AT₁ angiotensin II receptor and novel non-AT₁, non-AT₂ angiotensin II/III binding site in brainstem cardiovascular regulatory centers of the spontaneously hypertensive rat.
abstract: Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system that contributes to the elevation of blood pressure in this animal model. Physiological and pharmacological studies suggest that hyperactivation of brain AT₁ angiotensin receptors is a major pathophysiological factor. Consistent with these observations, radioligand binding studies indicate widespread up-regulation of brain angiotensin receptors in SHR. One key brainstem site in which AT₁ receptor stimulation appears to contribute to the elevated blood pressure in SHR is the rostral ventrolateral medulla (RVLM). However, no quantitative comparison of AT₁ receptor binding in the RVLM has been made in SHR versus normotensive rats. A novel, non-AT₁, non-AT₂ binding site, specific for angiotensins II and III, has recently been discovered in the brain. To determine if radioligand binding to either AT₁ receptors or this novel angiotensin binding site is altered in the RVLM and other caudal brainstem regions of SHR, a quantitative densitometric autoradiographic comparison of radioligand binding in SHR versus normotensive Wistar-Kyoto rats was made. In both the RVLM and caudal ventrolateral medulla (CVLM) as well as dorsomedial medulla (DMM), there was increased expression of AT₁ receptor binding in SHR (13%, 9%, and 23%, respectively). Conversely, expression of the novel, non-AT₁, non-AT₂, angiotensin II and III binding site was decreased in the RVLM and DMM of SHR (37% and 13%, respectively). This increased AT₁ receptor binding in the RVLM may contribute to the hypertension of SHR. Reduced radioligand binding to the novel, non-AT₁, non-AT₂, angiotensin binding site in the RVLM of SHR may indicate a role for this binding site to reduce blood pressure via its interactions with angiotensins II and III.
authors.affiliation: Biological Sciences, Northwest Missouri State University, Maryville, MO 64468, USA.
authors.forename: Erick A
authors.initials: EA
authors.lastname: Bourassa
authors.forename: Xiefan
authors.initials: X
authors.lastname: Fang
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
authors.forename: Robert C
authors.initials: RC
authors.lastname: Speth
mesh_terms: D000818:Animals; D001345:Autoradiography; D007091:Image Processing, Computer-Assisted; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012125:Respiratory Center / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1
references.citation: Hypertension. 2002 Oct;40(4):552-9
references.pmid: 12364362
references.citation: Pharmacol Ther. 2008 Dec;120(3):292-316
references.pmid: 18804122
references.citation: Brain Res. 2010 Jan 8;1306:69-76
references.pmid: 19835848
references.citation: Am J Physiol. 1996 Jun;270(6 Pt 2):R1317-23
references.pmid: 8764299
references.citation: Methods Mol Med. 2001;51:275-95
references.pmid: 21331724
references.citation: Physiol Genomics. 2004 Nov 17;19(3):255-61
references.pmid: 15383639
references.citation: Regul Pept. 2010 Jun 8;162(1-3):5-11
references.pmid: 20171994
references.citation: Eur J Pharmacol. 2008 Aug 20;590(1-3):87-92
references.pmid: 18571643
references.citation: Clin Exp Pharmacol Physiol. 1993 May;20(5):351-4
references.pmid: 8100748
references.citation: Peptides. 1986 Nov-Dec;7(6):1021-7
references.pmid: 3562315
references.citation: Clin Exp Pharmacol Physiol. 2002 Jan-Feb;29(1-2):103-11
references.pmid: 11906467
references.citation: Int Rev Exp Pathol. 1969;7:227-70
references.pmid: 4387955
references.citation: Brain Res. 1997 Oct 24;772(1-2):107-14
references.pmid: 9406962
references.citation: Hypertension. 1980 Jul-Aug;2(4):546-50
references.pmid: 6995295
references.citation: Neuroendocrinology. 2008;88(4):256-65
references.pmid: 18562784
references.citation: Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2961-6
references.pmid: 11087253
references.citation: Curr Hypertens Rep. 2003 Jun;5(3):262-8
references.pmid: 12724060
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):283-93
references.pmid: 18172611
references.citation: Brain Res. 2007 Apr 27;1143:83-91
references.pmid: 17306233
references.citation: Hypertension. 1992 May;19(5):475-81
references.pmid: 1568766
references.citation: J Mol Cell Cardiol. 1996 Feb;28(2):351-61
references.pmid: 8729067
references.citation: Brain Res. 2005 Mar 2;1036(1-2):70-6
references.pmid: 15725403
references.citation: Nature. 1977 Dec 1;270(5636):445-7
references.pmid: 593364
references.citation: J Hypertens. 1988 Jan;6(1):79-84
references.pmid: 3351297
references.citation: Nat Rev Neurosci. 2006 May;7(5):335-46
references.pmid: 16760914
references.citation: Nature. 1975 Nov 20;258(5532):267-8
references.pmid: 1202361
references.citation: Am J Physiol. 1984 Sep;247(3 Pt 2):R575-81
references.pmid: 6089597
references.citation: J Mol Med (Berl). 2008 Jun;86(6):715-22
references.pmid: 18385968
references.citation: Endocrine. 2010 Jun;37(3):442-8
references.pmid: 20960166
references.citation: J Renin Angiotensin Aldosterone Syst. 2001 Mar;2(1_suppl):S120-S124
references.pmid: 28095229
references.citation: Blood Press Suppl. 1994;5:21-6
references.pmid: 7889197
references.citation: Am J Physiol. 1991 May;260(5 Pt 2):R977-84
references.pmid: 1674644
references.citation: Pharmacology. 2007;80(2-3):166-76
references.pmid: 17551266
references.citation: Hypertension. 2010 Feb;55(2):207-13
references.pmid: 20038757
references.citation: Life Sci. 2008 Sep 12;83(11-12):421-5
references.pmid: 18692076
references.citation: Hypertension. 2006 Jun;47(6):1054-61
references.pmid: 16618838
references.citation: Am J Physiol. 1986 Feb;250(2 Pt 2):R193-8
references.pmid: 3946636
references.citation: Clin Exp Pharmacol Physiol. 2006 Aug;33(8):690-5
references.pmid: 16895541
references.citation: J Hypertens. 2007 Nov;25(11):2334-44
references.pmid: 17921830
references.citation: Br J Pharmacol. 2003 May;139(2):191-202
references.pmid: 12770924
references.citation: Brain Res Bull. 1998 Sep 1;47(1):17-28
references.pmid: 9766385
references.citation: Brain Res Bull. 2003 May 15;60(3):209-14
references.pmid: 12754082
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R1027-34
references.pmid: 16306161
references.citation: Am J Physiol. 1994 Jul;267(1 Pt 2):H259-66
references.pmid: 7914065
references.citation: Am J Physiol. 1999 Sep;277(3):R904-9
references.pmid: 10484510
references.citation: Jpn Circ J. 1963 Mar;27:282-93
references.pmid: 13939773
references.citation: J Appl Physiol (1985). 2002 May;92(5):2153-61
references.pmid: 11960969
references.citation: Mol Cell Endocrinol. 2009 Apr 29;302(2):167-75
references.pmid: 19027823
references.citation: Dev Psychobiol. 1991 Nov;24(7):507-19
references.pmid: 1797594