期刊
HYPERTENSION
卷 52, 期 4, 页码 708-714出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.108.116228
关键词
angiotensin II type 1 receptor; angiotensin II type 2 receptor; rostral ventrolateral medulla; sympathetic outflow
资金
- American Heart Association National Center [0635007N]
- National Institutes of Health [PO-1-HL-62222, RO-1-HL-38690]
Upregulation of angiotensin II type 1 receptors (AT(1)R) in the rostral ventrolateral medulla (RVLM) contributes to the sympathoexcitation in the chronic heart failure (CHF). However, the role of angiotensin II type 2 receptor (AT(2)R) is not clear. In this study, we measured AT(1)R and AT(2)R protein expression in the RVLM and determined their effects on renal sympathetic nerve activity, blood pressure, and heart rate in anesthetized sham and CHF rats. We found that (1) although AT(1)R expression in the RVLM was upregulated, the AT(2)R was significantly downregulated (CHF: 0.06 +/- 0.02 versus sham: 0.15 +/- 0.02, P < 0.05); (2) simultaneously stimulating RVLM AT(1)R and AT(2)R by angiotensin II evoked sympathoexcitation, hypertension, and tachycardia in both sham and CHF rats with greater responses in CHF; (3) stimulating RVLM AT(1)R with angiotensin II plus the specific AT(2)R antagonist PD123319 induced a larger sympathoexcitatory response than simultaneously stimulating AT(1)R and AT(2)R in sham rats, but not in CHF; (4) activating RVLM AT(2)R with CGP42112 induced a sympathoinhibition, hypotension, and bradycardia only in sham rats (renal sympathetic nerve activity: 36.4 +/- 5.1% of baseline versus 102 +/- 3.9% of baseline in artificial cerebrospinal fluid, P < 0.05); (5) pretreatment with 5,8,11,14-eicosatetraynoic acid, a general inhibitor of arachidonic acid metabolism, into the RVLM attenuates the CGP42112-induced sympathoinhibition. These results suggest that AT(2)R in the RVLM exhibits an inhibitory effect on sympathetic outflow, which is, at least partially, mediated by an arachidonic acid metabolic pathway. These data implicate a downregulation in the AT(2)R as a contributory factor in the sympathoexcitation in CHF.
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