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Enhanced Hemeoxygenase‐1 Signaling in the Rostral Ventrolateral Medulla Mediates a Critical Protective Role Against Genetically Elevated Blood Pressure in SHR Rats
Author(s) -
Nassar Noha N,
Li Guichu,
AbdelRahman Abdel A
Publication year - 2010
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.24.1_supplement.577.4
Subject(s) - rostral ventrolateral medulla , hemin , microinjection , medicine , endocrinology , heme oxygenase , blood pressure , chemistry , medulla oblongata , brainstem , sympathetic nervous system , spontaneously hypertensive rat , heme , heart rate , central nervous system , enzyme , biochemistry
Heme oxygenase (HO)‐derived carbon monoxide (CO) contributes to central regulation of blood pressure (BP). However, the few reported studies demonstrating reductions in BP following microinjection into the nucleus tractus solitarius of the HO substrate hemin, were carried out in anesthetized normotensive rats. We hypothesized that HO‐CO signaling is enhanced in the RVLM of conscious SHRs to prevent exacerbation of hypertension in this genetic model of hypertension. To test this hypothesis, we investigated the effects of intra‐RVLM hemin on BP, HR and RVLM neuronal norepinephrine (index of sympathetic activity; measured in real‐time by in vivo electrochemistry) in SHRs and their normotensive control WKY rats. Furthermore, the type of the specific HO isoenzyme implicated in the hypotensive response was investigated by administering the selective HO‐1 inhibitor zinc protoporphyrin IX (ZNPPIX) 30 minutes prior to hemin. Intra‐RVLM hemin elicited greater and longer‐lasting reductions in BP and RVLM NE in SHRs. These hemodynamic and electrochemical response, which suggest enhanced HO‐CO signaling in the RVLM of SHRs, were confirmed by the greater enzymatic activity of HO in SHRs than in WKY rats, Moreover, ZNPPIX, not only abolished the hemin‐evoked responses in either strain, albeit to a greater extent in SHRs, but also caused a marked increase in baseline pressure in SHRs. The findings suggest an exaggerated HO‐CO signaling, due to higher HO‐1 activity, in the RVLM of SHR, a brainstem area that controls sympathetic outflow. Such enhancement of HO‐CO signaling seems to serve as a protective mechanism that opposes further increases in BP in the SHR.