Publications (2)7.83 Total impact
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Article: Artificial microRNA interference targeting AT(1a) receptors in paraventricular nucleus attenuates hypertension in rats.
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ABSTRACT: Excessive sympathetic activity has a crucial role in the initiation and progression of chronic structural alterations in the heart and vessels associated with hypertension. Angiotensin II type 1a receptors (AT(1a)R) in paraventricular nucleus (PVN) are involved in sympathetic overdrive and hypertension. The present study was designed to investigate the cardiovascular beneficial effects of the AT(1a)R gene silence in the PVN in hypertension. The PVN microinjection of recombinant adenoviral vectors expressing either artificial microRNA (amiRNA) targeting AT(1a) receptors (Ad-miR-AT(1a)) or control microRNA (Ad-miR-Con) were carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. The vectors were labels with green fluorescent protein (GFP). The successful amiRNA interference was confirmed by the AT(1) receptors reduction and the GFP expression in the PVN. Significant depressor effects were observed from day 5 to day 20 after Ad-miR-AT(1a) treatment in SHR. Ad-miR-AT(1a) treatment decreased the ratio of left ventricular weight to body weight, cross-sectional areas of myocytes, myocardial fibrosis, media thickness, and the media/lumen ratio of the aorta and the mesenteric artery in SHR. The amiRNA interference reduced the basal sympathetic activity, cardiac sympathetic afferent reflex, plasma norepinephrine and plasma angiotensin II in SHR. These results indicate that amiRNA interference targeting AT(1a)R in the PVN decreases arterial blood pressure, blunts sympathetic activity and improves myocardial and vascular remodeling in SHR.Gene therapy 09/2011; 19(8):810-7. · 4.75 Impact Factor -
Article: Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats.
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ABSTRACT: This study was to determine the roles of inflammatory cytokines in paraventricular nucleus (PVN) in modulating sympathetic activity, blood pressure and cardiac sympathetic afferent reflex (CSAR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats with bilateral sinoaortic denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The levels of inflammatory cytokines were measured with ELISA. The PVN microinjection of pro-inflammatory cytokines (PIC), tumour necrosis factor (TNF)-α or interleukin (IL)-1β, increased the baseline MAP and RSNA, and enhanced the CSAR. Anti-inflammatory cytokines (AIC), IL-4 or IL-13, in the PVN only increased the baseline MAP. In the rats pretreated with TNF-α or IL-1β but not in the rats pretreated with IL-4 or IL-13, sub-response dose of angiotensin II caused significant increases in the MAP and RSNA and enhancement in the CSAR. AT(1) receptor antagonist losartan in the PVN attenuated the effects of angiotensin II, TNF-α and IL-1β, but not the effects of IL-4 and IL-13. Stimulation of cardiac sympathetic afferents with epicardial application of BK increased the levels of TNF-α, IL-1β but not IL-4 in the PVN. TNF-α or IL-1β in the PVN increases blood pressure and sympathetic outflow and enhances the CSAR, which is partially dependent on the AT(1) receptors, while IL-4 or IL-13 in the PVN only increases blood pressure. There is a synergetic effect of Ang II with TNF-α or IL-1β on blood pressure, sympathetic activity and CSAR.Acta Physiologica 04/2011; 203(2):289-97. · 3.09 Impact Factor
