Microinjection of resveratrol into rostral ventrolateral medulla decreases sympathetic vasomotor tone through nitric oxide and intracellular Ca2+ in anesthetized male rats

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 mu mol/L, 0.2 mu L) into the RVLM dose dependently decreased BP, HR and RSNA. Pretreatment with an anti-estrogen tamoxifen (100 mu mol/L, 0.2 mu L) did not affect the effects of RES. Pretreatment with N-G-nitro-L-arginine methyl ester (100 mu mol/L, 0.2 mu L), 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 mu L), 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 mu L), 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.