Long-term administration of tempol attenuates postinfarct ventricular dysfunction and sympathetic activity in rats.

Abstract

The purpose of this study was to determine whether the long-term administration of tempol attenuates postinfarct ventricular dysfunction and sympathetic activity in rats. Myocardial infarction (MI) was induced by left descending coronary artery ligation. Tempol was orally administered in drinking water (2 mmol/L), which was initiated 4 h after infarction and continued for 6 weeks. Tempol prevented not only the increases in left ventricular end-diastolic pressure and volume but also the decreases in ejection fraction and peak velocities of contraction in MI rats. The treatment normalized the increased renal sympathetic nerve activity (RSNA) and plasma norepinephrine level, as well as the enhanced cardiac sympathetic afferent reflex (CSAR; an excitatory cardiovascular reflex partially contributing to the sympathetic activation in chronic heart failure) and the RSNA responses to microinjection of angiotensin II into paraventricular nucleus in MI rats. Furthermore, tempol prevented the increased AT(1) receptor protein expression and superoxide anion level in both paraventricular nucleus and rostral ventrolateral medulla in MI rats. In conclusion, long-term administration of tempol attenuates ventricular dysfunction and normalizes sympathetic neural control in MI rats. The normalization of the CSAR, levels of superoxide anions and AT(1) receptor expression, and the response to angiotensin II in the paraventricular nucleus and rostral ventrolateral medulla may partially contribute to the beneficial effects of tempol on central sympathetic control.

• Authors: Zhen Shi, Ai-Dong Chen, Yao Xu, Qi Chen, Xing-Ya Gao, Wei Wang, Guo-Qing Zhu
• Journal: Pflugers Archiv : European journal of physiology (Pflugers Arch) Vol. 458 Issue 2 Pg. 247-57 (Jun 2009) ISSN: 1432-2013 [Electronic] Germany
• PMID: 19132383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic N-Oxides
• Spin Labels
• Superoxides
• Angiotensin II
• tempol
• Norepinephrine

Topics

• Angiotensin II (physiology)
• Animals
• Cyclic N-Oxides (therapeutic use)
• Male
• Medulla Oblongata (physiology)
• Myocardial Infarction (drug therapy)
• Norepinephrine (blood)
• Paraventricular Hypothalamic Nucleus (drug effects)
• Rats
• Rats, Sprague-Dawley
• Spin Labels
• Superoxides (metabolism)
• Sympathetic Nervous System (drug effects, physiology)
• Ventricular Dysfunction (drug therapy)