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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/R1364    most recent 00149.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zheng, H. Articles by Patel, K. P. PubMed PubMed Citation Articles by Zheng, H. Articles by Patel, K. P.

Articles

Enhanced angiotensin-mediated excitation of renal sympathetic nerve activity within the paraventricular nucleus of anesthetized rats with heart failure

¹Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska; and ²Division of Basic Biomedical Science, College of Medicine, University of South Dakota, Vermillion, South Dakota

Submitted March 13, 2009 ; accepted in final form August 21, 2009

Chronic heart failure (HF) is characterized by increased sympathetic drive. Enhanced angiotensin II (ANG II) activity may contribute to the increased sympathoexcitation under HF condition. The present study examined sympathoexcitation by 1) the effects of ANG II in the paraventricular nucleus (PVN) on renal sympathetic nerve activity (RSNA), and 2) the altered ANG II type 1 (AT₁) receptor expression during HF. Left coronary artery ligation was used to induce HF. In the anesthetized Sprague-Dawley rats, microinjection of ANG II (0.05–1 nmol) into the PVN increased RSNA, mean arterial pressure (MAP), and heart rate (HR) in both sham-operated and HF rats. The responses of RSNA and HR were significantly enhanced in rats with HF compared with sham rats (RSNA: 64 ± 8% vs. 33 ± 4%, P < 0.05). Microinjection of AT₁ receptor antagonist losartan into the PVN produced a decrease of RSNA, MAP, and HR in both sham and HF rats. The RSNA and HR responses to losartan in HF rats were significantly greater (RSNA: –25 ± 4% vs. –13 ± 1%, P < 0.05). Using RT-PCR and Western blot analysis, we found that there were significant increases in the AT₁ receptor mRNA (186 ± 39%) and protein levels (88 ± 20%) in the PVN of rats with HF (P < 0.05). The immunofluorescence of AT₁ receptors was significantly higher in the PVN of rats with HF. These data support the conclusion that an increased angiotensinergic activity on sympathetic regulation, due to the upregulation of ANG II AT₁ receptors within the PVN, may contribute to the elevated sympathoexcitation that is observed during HF.

angiotensin; sympathetic activity; blood pressure; AT₁ receptor