title: Involvement of enhanced cardiac sympathetic afferent reflex in sympathetic activation in early stage of diabetes.
abstract: Cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation. The present study was designed to investigate the contribution of enhanced CSAR to sympathetic activation in the early stage of diabetes and the involvement of AT(1) receptors in the paraventricular nucleus (PVN). Diabetes was induced by a single intravenous injection of streptozotocin in rats. Acute experiments were carried out under anesthesia after 3 wk. The CSAR was evaluated by the responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin or bradykinin. Sympathetic activity and CSAR were enhanced in diabetic rats. Plasma norepinephrine and angiotensin II were increased, but the transient receptor potential vanilloid 1 (TRPV1) in the left ventricle wall was not significantly increased in diabetic rats. Pericardial injection of resiniferatoxin to desensitize cardiac afferents or PVN microinjection of lidocaine attenuated the CSAR and decreased the RSNA and MAP in diabetic rats. The AT(1) receptor expression in the PVN increased in diabetic rats. Angiotensin II in the PVN caused greater increases in the RSNA and MAP and enhancement in the CSAR in diabetic rats, which were abolished by the losartan pretreatment. Losartan decreased the RSNA and MAP and attenuated the CSAR in diabetic rats but not in control rats. These results indicate that the CSAR is enhanced in the early stage of diabetic rats, which contributes to the sympathetic activation. AT(1) receptors in the PVN are involved in the enhanced CSAR in diabetic rats.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Xiong
authors.forename: Zhi-Dan
authors.initials: ZD
authors.lastname: Fan
authors.forename: Xian-Bing
authors.initials: XB
authors.lastname: Gan
authors.forename: Xing-Ya
authors.initials: XY
authors.lastname: Gao
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
mesh_terms: D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004224:Diterpenes / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D008012:Lidocaine / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D050916:TRPV Cation Channels / Q000032:analysis
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000889:Anti-Arrhythmia Agents; D004224:Diterpenes; D044140:Receptor, Angiotensin, Type 1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D000804:Angiotensin II; D008012:Lidocaine; C024353:resiniferatoxin; D019808:Losartan; D002211:Capsaicin; D001920:Bradykinin; D009638:Norepinephrine