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

Acta Pharmacol Sin. 2008 Aug;29(8):906-12. doi: 10.1111/j.1745-7254.2008.00827.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia
  • Animals
  • Blood Pressure / drug effects
  • Calcium Signaling / drug effects*
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Heart Rate / drug effects
  • Male
  • Medulla Oblongata / physiology*
  • Microinjections
  • Muscle Tonus / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / innervation
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation / drug effects
  • Resveratrol
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*
  • Sympathetic Nervous System / drug effects*

Substances

  • Enzyme Inhibitors
  • Stilbenes
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Resveratrol