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Intrathecal injection of TRPV1 shRNA leads to increases in blood pressure in rats

AIM: The transient receptor potential vanilloid type 1 (TRPV1) channels have been implicated to play a role in blood pressure regulation. However, contribution of tissue specific TRPV1 to blood pressure regulation is largely unknown. Here, we test the hypothesis that TRPV1 expressed in dorsal root ganglia (DRG) of lower thoracic and upper lumbar segments (T8-L3) of the spinal cord and their central and peripheral terminals constitutes a counter regulatory mechanism preventing the increases in blood pressure. METHODS: The expression of TRPV1 was knocked down by intrathecal injection of TRPV1 short-hairpin RNA (shRNA) in rats. Systolic blood pressure and mean arterial pressure (MAP) were recorded. The level of TRPV1 and tyrosine hydroxylase (TH) was measured by Western blot. RESULTS: Intrathecal injection of TRPV1 shRNA (6 mug kg(-1) day(-1) ) for 3 days increased systolic blood pressure and MAP when compared to rats that received control shRNA (control shRNA: 112 +/- 2 vs. TRPV1 shRNA: 123 +/- 2 mmHg). TRPV1 expression was suppressed in T8-L3 segments of dorsal horn and DRG as well as mesenteric arteries of rats given TRPV1 shRNA. Contents of TH, a marker of sympathetic nerves, were increased in mesenteric arteries of rats treated with TRPV1 shRNA. Pretreatment with the alpha1-adrenoceptor blocker, prazosin (1 mg kg(-1) day(-1) , p.o.), abolished the TRPV1 shRNA-induced pressor effects. CONCLUSION: Our data show that selective knockdown of TRPV1 expressed in DRG of T8-L3 segments of the spinal cord and their central and peripheral terminals increases blood pressure, suggesting that neuronal TRPV1 in these segments possesses a tonic anti-hypertensive effect possibly via suppression of the sympathetic nerve activity

Keywords : administration & dosage,Animals,antagonists & inhibitors,Arteries,biosynthesis,blood,Blood Pressure,Blotting,Western,drug effects,Ganglia,Spinal,Gene Knockdown Techniques,genetics,Immunohistochemistry,Injections,Spinal,Male,metabolism,methods,Pressure,Rats,Rats,Wistar,RNA,Small Interfering,Spinal Cord,Sympathetic Nervous System,TRPV Cation Channels,, Injection,Trpv1,Shrna,Leads, frozen shoulder causes

Date of Publication : 2011 Sep

Authors : Yu SQ;Wang DH;

Organisation : Department of Medicine, Michigan State University, East Lansing, USA

Journal of Publication : Acta Physiol (Oxf)

Pubmed Link :

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