title: Pro-inflammatory cytokines in paraventricular nucleus mediate the cardiac sympathetic afferent reflex in hypertension.
abstract: Our previous studies showed that pro-inflammatory cytokines (PIC) in the hypothalamic paraventricular nucleus (PVH) potentiated the cardiac sympathetic afferent reflex (CSAR) in normotensive rats. This study determined whether PIC in the PVH mediate enhanced CSAR and over-excited sympathetic activity in spontaneously hypertensive rats (SHR). CSAR was evaluated by renal sympathetic nerve activity (RSNA) response to epicardial application of bradykinin (BK). Inflammatory cytokine levels were measured with ELISA. In both SHR and normotensive Wistar-Kyoto (WKY) rats, PVH microinjection of PIC, tumour necrosis factor (TNF)-α or interleukin (IL)-1β, increased the baseline mean arterial blood pressure (MAP), RSNA and the CSAR, but anti-inflammatory cytokines (AIC), IL-4 or IL-13, only increased the baseline MAP. PVH pretreatment with PIC caused sub-response dose of angiotension (Ang) II to produce baseline RSNA and MAP elevation and the CSAR enhancement responses, but AIC (IL-4 or IL-13) did not. PVH microinjection of PIC induced greater changes in SHR than in normotensive WKY rats. In addition, stimulation of cardiac sympathetic afferents with epicardial application of BK increased PIC levels in the PVH in both SHR and WKY rats. Intrapericardial administration of resiniferatoxin (RTX) which abolished the CSAR decreased the PIC levels in the PVH to a lower level in SHR than in WKY rats. These results suggest that the increased PIC in the PVH in SHR mediated the increased sympathetic outflow and the enhanced CSAR, and that the augmented effect of Ang II in the PVH on sympathetic activity and the CSAR is also associated with PIC.
authors.affiliation: Department of Physiology, Binzhou Medical University, Yantai 264003, China. Electronic address: zhen_shizhen@163.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Physiology, Binzhou Medical University, Yantai 264003, China.
authors.forename: Shu-jun
authors.initials: SJ
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Binzhou Medical University, Yantai 264003, China.
authors.forename: Gui-hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Department of Physiology, Binzhou Medical University, Yantai 264003, China.
authors.forename: Ai-li
authors.initials: AL
authors.lastname: Xu
authors.affiliation: Department of Physiology, Binzhou Medical University, Yantai 264003, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D018793:Interleukin-13 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000294:innervation; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000503:physiopathology*; D011897:Random Allocation; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002120:Calcium Channel Agonists; D016207:Cytokines; D004224:Diterpenes; C000594089:IL1B protein, rat; D018793:Interleukin-13; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D015847:Interleukin-4; C024353:resiniferatoxin; D001920:Bradykinin
keywords: Blood pressure; Paraventricular nucleus; Pro-inflammatory cytokines; Sympathetic activity