• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.477-486
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• 2011

The purpose of the present study was to investigate whether polyphenol-rich fraction extracted from fruit wine of Rubus coreanum M (PCRC) can affect the contractility of the thoacic aortic strips isolated from spontaneously hypertensive rats (SHRs), and to clarify its mechanism of action. PCRC (200-800 ${\mu}g/mL$) concentration-depenedently blocked phenylephrine (10 ${\mu}M$)-induced contractile responses of the isolated aortic strips of SHRs. PCRC (400 ${\mu}g/mL$), added in to bath medium, also depressed the contractile active tension evoked by both phenylephrine (3 and 10 ${\mu}M$) and high potassium (25 and 56 mM). In the simultaneous presence of PCRC (400 ${\mu}g/mL$) and L-NAME (a selective inhibitor of NO synthase, 300 ${\mu}M$), the contractile responses evoked by phenylephrine and high $K^+$ were recovered to considerable level of the corresponding control contractility compared with those effects of PCRC-treatment alone. However, in the simultaneous presence of indomethacin (10 ${\mu}M$, a selective cyclooxygenase inhibitor) and PCRC (400 ${\mu}g/mL$), they were not affected. In the endothelium-denuded aortic strips by CHAPS-treatment, PCRC did not affect the contractile responses induced by phenylephrine or high potassium. Interestingly, PCRC (1.0, 3.0 and 10.0 mg/kg/30 min, i.v., respectively) dose-dependently suppressed norepiphrine-induced vasopressor responses in anesthetized SHRs. Collectively, we concluded that PCRC causes vasorelaxation in the thoracic aortic strips with intact endothelium of SHRs at least partly by the increased NO production through the activation of NO synthase of vascular endothelium, but not through the activation of cyclooxygenase. These results suggest that PCRC might be helpful to prevent or alleviate cardiovascular diseases, including hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.517-526
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• 2009

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC $(20\sim180\;{\mu}g/ml)$ perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC $(60\;{\mu}g/ml)$, the CA secretory responses to veratridine (a selective $Na^+$ channel activator $(10\;{\mu}M)$, Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, $10\;{\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, $10\;{\mu}M$) were significantly reduced, respectively. In the simultaneous presence of PCRC $(60\;{\mu}g/ml)$ and L-NAME (an inhibitor of NO synthase, $30\;{\mu}M$), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high $K^+$, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC $(60\;{\mu}g/ml)$ was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.