AT1 receptor mRNA antisense normalizes enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure

American Journal of Physiology. Heart and Circulatory Physiology
Guo-Qing ZhuWei Wang

Abstract

Previous studies showed that the cardiac sympathetic afferent reflex (CSAR) is enhanced in dogs and rats with chronic heart failure (CHF) and that central ANG II type 1 receptors (AT(1)R) are involved in this augmented reflex. The aim of this study was to determine whether intracerebroventricular administration and microinjection of antisense oligodeoxynucleotides targeted to AT(1)R mRNA would attenuate the enhanced CSAR and decrease resting renal sympathetic nerve activity (RSNA) in rats with coronary ligation-induced CHF. The CSAR was elicited by application of bradykinin to the epicardial surface of the left ventricle. Reflex responses to epicardial administration of bradykinin were enhanced in rats with CHF. The response to bradykinin was determined every 50 min after intracerebroventricular administration (lateral ventricle) or microinjection (into paraventricular nucleus) of antisense or scrambled oligonucleotides to AT(1)R mRNA. AT(1)R mRNA and protein levels in the paraventricular nucleus were significantly reduced 5 h after administration of antisense. Antisense significantly decreased resting RSNA and normalized the enhanced CSAR responses to bradykinin in rats with CHF. Scrambled oligonucleotides did not alter restin...Continue Reading

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Jan 10, 2009·Pflügers Archiv : European journal of physiology·Zhen ShiGuo-Qing Zhu
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