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Blockade of glutamate receptors abolishes the sensitization of the angiotensin II‐elicited hypertensive response in rats
Author(s) -
Xue Baojian,
Beltz Terry G.,
Guo Fang,
Johnson Alan Kim
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.732.1
Subject(s) - sensitization , endocrinology , angiotensin ii , medicine , blockade , nmda receptor , downregulation and upregulation , renin–angiotensin system , glutamate receptor , receptor , chemistry , pharmacology , neuroscience , biology , blood pressure , biochemistry , gene
Angiotensin (ANG) II‐elicited hypertension is associated with neuroplasticity of glutamate receptors (GluRs) in the brain nuclei involved in blood pressure regulation including the lamina terminalis (LT) and hypothalamic paraventricular nucleus (PVN). Using the Induction‐Delay‐Expression (IND‐DEL‐EXP) experimental paradigm, our previous studies demonstrated that administration of a subpressor dose of angiotensin (ANG) II (10 ng/kg/min) during IND sensitizes subsequent ANG II (120 ng/kg/min)‐elicited hypertension during EXP. This subpressor dose of ANG II also induced increased phosphorylation of the GluN1 subunit in LT structures. The present study investigated whether the blockade of GluRs during IND abolishes sensitization of subsequent ANG II‐elicited hypertension. We found in the rat that the sensitized ANG II hypertensive response produced by a subpressor of dose ANG II given during IND was blocked by co‐administration of either MK‐801 (sc) or of (2R)‐amino‐5‐phosphonovaleric acid (a.k.a. AP5, icv). Moreover, ANG II‐induced upregulation of mRNA expression of several renin‐angiotensin system (RAS) and proinflammatory components in the LT and PVN was also attenuated. These results indicate that central nervous system (CNS) neuroplasticity associated with hypertension response sensitization requires NMDA‐R activation. Furthermore, the inhibitory effect of NMDA‐R blockade on hypertension response sensitization is associated with reducing upregulation of prohypertensive components of the brain RAS and of inflammatory mediators in the CNS. Support or Funding Information the National Institutes of Health grants HL‐14388, HL‐84207 and HL‐98207. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .