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Cytokine blockade attenuates sympathoexcitation in heart failure: cross-talk between nNOS, AT-1R and cytokines in the hypothalamic paraventricular nucleus.
Eur J Heart Fail. 2008 Jul; 10(7):625-34.EJ

Abstract

OBJECTIVE

To investigate evidence for the interplay between cytokines, angiotensin II and nNOS in the paraventricular nucleus (PVN), for regulating sympathetic outflow in a rat model of CHF.

METHODS AND RESULTS

Heart failure was induced in Sprague-Dawley rats by coronary artery ligation. One group of rats was treated with pentoxifylline (PTX, 30 mg/kg IP), a cytokine blocker, or vehicle, for 5 weeks. Another group of rats was pre-treated with PTX before coronary ligation to study prior cytokine blocking effect on survival. Both groups were combined in the analysis. Echocardiography demonstrated an increase in LV end-diastolic pressure and Tei index after 5 weeks in CHF rats. ELISA revealed a significant increase in plasma TNF-alpha and IL-1beta in CHF rats. Inducible NOS (iNOS) and angiotensin receptor-type 1 (AT-1R) mRNA expressions were increased, while neuronal NOS (nNOS) was decreased in the PVN of CHF rats; these changes were reversed by PTX. PTX treatment also decreased plasma norepinephrine and epinephrine levels and improved baroreflex control of renal sympathoexcitation in CHF rats. Immunohistochemistry revealed elevated 3-nitrotyrosine formation in the heart and the PVN of CHF rats, but not in PTX treated rats.

CONCLUSION

PTX decreased both peripheral and central cytokine expression, alleviated nitric oxide dysregulation, and inhibited the formation of peroxynitrite in the PVN resulting in decreased sympathoexcitation in CHF rats.

Authors+Show Affiliations

Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA-70803, United States.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18550427

Citation

Guggilam, Anuradha, et al. "Cytokine Blockade Attenuates Sympathoexcitation in Heart Failure: Cross-talk Between nNOS, AT-1R and Cytokines in the Hypothalamic Paraventricular Nucleus." European Journal of Heart Failure, vol. 10, no. 7, 2008, pp. 625-34.
Guggilam A, Patel KP, Haque M, et al. Cytokine blockade attenuates sympathoexcitation in heart failure: cross-talk between nNOS, AT-1R and cytokines in the hypothalamic paraventricular nucleus. Eur J Heart Fail. 2008;10(7):625-34.
Guggilam, A., Patel, K. P., Haque, M., Ebenezer, P. J., Kapusta, D. R., & Francis, J. (2008). Cytokine blockade attenuates sympathoexcitation in heart failure: cross-talk between nNOS, AT-1R and cytokines in the hypothalamic paraventricular nucleus. European Journal of Heart Failure, 10(7), 625-34. https://doi.org/10.1016/j.ejheart.2008.05.004
Guggilam A, et al. Cytokine Blockade Attenuates Sympathoexcitation in Heart Failure: Cross-talk Between nNOS, AT-1R and Cytokines in the Hypothalamic Paraventricular Nucleus. Eur J Heart Fail. 2008;10(7):625-34. PubMed PMID: 18550427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokine blockade attenuates sympathoexcitation in heart failure: cross-talk between nNOS, AT-1R and cytokines in the hypothalamic paraventricular nucleus. AU - Guggilam,Anuradha, AU - Patel,Kaushik P, AU - Haque,Masudul, AU - Ebenezer,Philip J, AU - Kapusta,Daniel R, AU - Francis,Joseph, Y1 - 2008/06/11/ PY - 2008/01/04/received PY - 2008/04/06/revised PY - 2008/05/06/accepted PY - 2008/6/14/pubmed PY - 2008/12/17/medline PY - 2008/6/14/entrez SP - 625 EP - 34 JF - European journal of heart failure JO - Eur. J. Heart Fail. VL - 10 IS - 7 N2 - OBJECTIVE: To investigate evidence for the interplay between cytokines, angiotensin II and nNOS in the paraventricular nucleus (PVN), for regulating sympathetic outflow in a rat model of CHF. METHODS AND RESULTS: Heart failure was induced in Sprague-Dawley rats by coronary artery ligation. One group of rats was treated with pentoxifylline (PTX, 30 mg/kg IP), a cytokine blocker, or vehicle, for 5 weeks. Another group of rats was pre-treated with PTX before coronary ligation to study prior cytokine blocking effect on survival. Both groups were combined in the analysis. Echocardiography demonstrated an increase in LV end-diastolic pressure and Tei index after 5 weeks in CHF rats. ELISA revealed a significant increase in plasma TNF-alpha and IL-1beta in CHF rats. Inducible NOS (iNOS) and angiotensin receptor-type 1 (AT-1R) mRNA expressions were increased, while neuronal NOS (nNOS) was decreased in the PVN of CHF rats; these changes were reversed by PTX. PTX treatment also decreased plasma norepinephrine and epinephrine levels and improved baroreflex control of renal sympathoexcitation in CHF rats. Immunohistochemistry revealed elevated 3-nitrotyrosine formation in the heart and the PVN of CHF rats, but not in PTX treated rats. CONCLUSION: PTX decreased both peripheral and central cytokine expression, alleviated nitric oxide dysregulation, and inhibited the formation of peroxynitrite in the PVN resulting in decreased sympathoexcitation in CHF rats. SN - 1388-9842 UR - https://www.unboundmedicine.com/medline/citation/18550427/Cytokine_blockade_attenuates_sympathoexcitation_in_heart_failure:_cross_talk_between_nNOS_AT_1R_and_cytokines_in_the_hypothalamic_paraventricular_nucleus_ L2 - https://doi.org/10.1016/j.ejheart.2008.05.004 DB - PRIME DP - Unbound Medicine ER -