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Blunted Arterial Baroreflex Sensitivity: A Contributor to Hypertension in Angiotensin Type 2 Receptor Knockout Mice
Author(s) -
Gao Juan,
Chao Jie,
Walther Thomas,
Gembardt Florian,
Zucker Irving H.,
Gao Lie
Publication year - 2012
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.26.1_supplement.893.7
Subject(s) - baroreflex , endocrinology , medicine , losartan , angiotensin ii , chemistry , superoxide , enos , renin–angiotensin system , blood pressure , nitric oxide synthase , nitric oxide , heart rate , biochemistry , enzyme
AT2R deficient (KO) mice have been reported to exhibit hypertension, which, we hypothesized, is related to the loss of sympathetic inhibition by the AT2R. In this experiment, we found that, compared to wild type (WT) mice: (1) KO mice exhibited higher blood pressure (MAP) (KO 85.0 ¡À 3.7 vs WT 74.7 ¡À 3.8 mmHg, p < 0.05) and renal sympathetic nerve activity (RSNA) (KO 31.3 ¡À 4.8 vs WT 18.5 ¡À 0.9 % max, p < 0.05); (2) Baroreflex sensitivity was blunted in KO mice (Gmax for HR: KO 2.7 ¡À 1.1 vs WT 8.4 ¡À 2.7 bpm/mmHg, p < 0.05; Gmax for RSNA: KO −1.2 ¡À 1.7 vs WT 12.9 ¡À 1.3 % max/mmHg, p < 0.05); (3) In KO mice, ICV Ang II evoked bigger pressor and sympatho‐excitatory responses, and ICV losartan (AT1R antagonist) induced a bigger fall of MAP and RSNA; (4) DHE staining showed a higher superoxide product in nucleus tractus solitarius (NTS) of KO mice; (5) Western blot analysis indicated higher AT1R, SOD1, nNOS, and eNOS protein expressions in the NTS of KO mice. These results demonstrate an impaired baroreflex function in AT2R deficient mice, which might evoke sympatho‐excitation and therefore hypertension. Our data also imply that impairment of baroreflex function in KO mice may be related to increased superoxide in the NTS via an upregulated AT1R expression and enhanced Ang II responses. The upregulated SOD1, nNOS, and eNOS protein expressions in NTS of AT2R KO mice may represent a compensatory mechanism to locally accumulated superoxide and deficient NO.