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The present study aimed to reveal the effects of urotensin II (UII) on sympathetic vasomotor tone in the rostral ventrolateral medulla (RVLM). UII (0.3, 3, and 30 nmol/L, 50 nL) was microinjected into the RVLM. Blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured to determine the sympathetic vasomotor tone. BP, HR, and RSNA were simultaneously recorded after drugs had been microinjected into the RVLM. Microinjection of UII (0.3, 3, and 30 nmol/L, 50 nL) into the RVLM significantly increased BP, HR, and RSNA. Pretreatment with BIM23127 (300 nmol/L, 50 nL), a potent antagonist of the UII receptor GPR14, abolished the effect of UII. Previous microinjection of PD98059 (25 μmol/L, 50 nL), an inhibitor of ERK, significantly suppressed the effects of UII. Preinjection of an inhibitor of the N-type Ca 2+ channel, ω-conotoxin GVIA (50 nmol/L, 50 nL), inhibited the effects of UII. The present study demonstrated that microinjection of UII into the RVLM significantly increased sympathetic vasomotor tone, which was mediated by the GPR14/ERK/N-type Ca 2+ channel pathway. UII may become a novel therapeutic target for autonomic nervous system regulation, especially in hypertension.

Aim: To define the effect of resveratrol (RES) on the central regulation of blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA)., Methods: RES was microinjected into the rostral ventrolateral medulla (RVLM), and BP, HR, and RSNA were recorded simultaneously in anesthetized rats., Results: A microinjection of RES (20, 40, and 80 micromol/L, 0.2 microL) into the RVLM dose dependently decreased BP, HR, and RSNA. Pretreatment with an anti-estrogen tamoxifen (100 micromol/L, 0.2 microL) did not affect the effects of RES. Pretreatment with NG-nitro- L-arginine methyl ester (100 micromol/L, 0.2 microL), an inhibitor of nitric oxide (NO) synthase, could completely abolish the effect of RES. A prior microinjection of Bay K8644 (500 nmol/L, 0.2 microL), an agonist of calcium channels, could also abrogate the effect of RES. Prior administration of a potent inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L, 0.2 microL), could partially attenuate the inhibitory effect of RES., Conclusion: The results suggest that a microinjection of RES into the RVLM inhibits BP, HR, and RSNA. The effects may be mediated by NO synthesis and a decrease in Ca2+ influx, in which protein tyrosine kinase is involved.