Effects of homocysteine and puerarin on coronary vasomotor responses
Effects of homocysteine and puerarin on coronary
vasomotor responses Submitted by Dennis King Yin Yeung
for the degree of Master of Philosophy at The University of Hong Kong
in August 2003
The present study addresses the vascular effects of short-term exposure to
homocysteine and puerarin in porcine coronary artery rings. In some
experiments, the endothelium of porcine coronary artery ring was disrupted by
perfusion of Triton-X100 (0.5 %) for 30 seconds. Changes in isometric tension
force were measured in organ baths.
Vascular responses to
endothelium-dependent relaxing agents, bradykinin and the calcium ionophore
A23187, endothelium-independent relaxing agents, sodium nitroprusside and
cromakalim, also to contracting agents potassium chloride (KCI),
5-hydroxytryptamine, the thromboxane A2 analogue U46619 and endothelin-1
were investigated in the presence and/or absence of homocysteine and puerarin.
An elevated level of homocysteine represents a strong and independent risk
factor for many cardiovascular diseases. The vascular endothelium has been
shown to be the initial target of homocysteine. In the present study,
endothelium-dependent relaxation to bradykinin and A23187, but not
endothelium-independent relaxation to sodium nitroprusside was attenuated by homocysteine (1 mM and 5 mM). This impairment of endothelium-dependent
relaxation by homocysteine was more profound with increasing exposure time.
The vasoconstrictions to the receptor-mediated agents, 5-hydroxytryptamine, U46619 and endothelin-1, but not to the depolarising agent KCI, were appreciably inhibited after incubation with homocysteine (1 mM) for 30 minutes. In summary,
homocysteine exerts inhibitory actions on both vasodilation and vasoconstriction
regardless of the signaling pathway. These inhibitions, however, demonstrate the dependency of exposure time.
Radix Puerariae, is a Chinese medicinal herb that is widely used in China for the
management of cardiovascular disorders. The major bioactive isoflavonoid
derivative isolated from this herb is puerarin, which has been demonstrated to contribute to the cardioprotective role of Radix Puerariae through the promotion of
vasodilation and inhibition of vasoconstriction. Therefore, the focus of my study
was to elucidate the intracellular mechanisms responsible for the vascular actions
of puerarin. At a concentration with no direct vascular effects (10M ), puerarin significantly reduced vasoconstrictions to 5-hydroxytryptamine and endothelin-1, without affecting the responses to KCI, following short-term exposure (30 minutes). Short-term exposure to puerarin (10M ) also resulted in significant potentiation of the vasodilation by the endothelium-independent agents, cromakalim and sodium nitroprusside. Endothelium-dependent relaxation to bradykinin and A23187 were unaffected by puerarin. The potentiating actions of puerarin persisted following the inhibition of nitric oxide synthase with L-NAME and in endothelium-disrupted porcine coronary arterial rings. While cyclic AMP analogue 8-bromo-cyclic AMP and the protein kinase A activator Sp-cyclic AMPS mimicked the enhancement of endothelium-independent relaxation by puerarin however, the cyclic GMP analogue 8-bromo-cyclic GMP had no effect on
relaxation to sodium nitroprusside and cromakalim. Furthermore, the cyclic
AMP-dependent protein kinase A inhibitor Rp-cyclic AMPS, but not the cyclic GMP antagonist Rp-8-bromo-cyclic GMPS, effectively reversed the enhancing
actions of puerarin on vasodilation to sodium nitroprusside. Taken together,
these data indicate that puerarin can acutely modulate vasoconstriction and vasodilation in porcine coronary arteries. The present findings also suggest that the beneficial effect of puerarin on endothelium-dependent relaxation is mediated via cyclic AMP-dependent cascade and possibly Gs protein.
Word count = 482
School:The University of Hong Kong
School Location:China - Hong Kong SAR
Source Type:Master's Thesis
Keywords:homocysteine physiological effect arrowroot therapeutic use swine cardiovascular system of drugs on
Date of Publication:01/01/2004