Elmowafy A M, Laila A, Abou Zeid.
Resveratrol activates the kinase-g system in human coronary smooth muscle cells via a nongenomic, Estrogen-independent mechanism.
J Basic Applied Sci Jan ;2(2):71-8.

Resveratrol (RSVL), a polyphenolic phytoestrogen in grapes, confers multifaceted cardiovascular benefits. The cellular and molecular basis of RSVL actions has been largely undefined. Currently, in human coronary smooth muscle cells (HCSMCs), RSVL markedly (3.2 fold) enhanced cGMP formation (t1/2: 6.3 min, EC50: 1.8 uM) and stimulated kinase-G activity (4 fold). By contrast, RSVL had no effect on cAMP or PKA activity in these cells. The RSVL-enhanced cGMP/kinase-G activity was not abrogated by either of the phosphodiesterase-inhibitors (zaprinast, 10 uM, IBMX, 0.5mM), the nitric oxide synthase-inhibitor (L-NMMA, 10 uM), or the soluble guanylyl cyclase (sGC)-inhibitor (ODQ, 10 uM). In membrane preparations from HCSMCs, RSVL activated GC in the particulate-, but not in the soluble- membrane fraction. Similar effects were due to the specific particulate-GC (pGC) agonist atrial natriuretic peptide (ANP, 0.1-1 uM). By contrast, the nitric oxide donor, SNAP (1-10 uM) stimulated GC only in the soluble fraction. Responses to RSVL were insensitive to the estrogen receptor blockers, tamoxifen and ICI-182,780. Conversely, pretreatment with the PKC activator, PMA (0.1 uM), a known desensitizer of pGC, markedly blunted the RSVL-enhanced GC-activity. These findings demonstrate that RSVL triggers a pGC-mediated stimulation of protein kinase-G in human coronary smooth muscle cells. This pathway appears to be independent of the conventional estrogen machinery and supports both vasodilatory and anti-atherogenic actions for RSVL.

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