Acetylcholine vascular smooth muscle effects

Activation of endothelial cell muscarinic receptors by acetylcholine (Ach) releases endothelium-derived relaxing factor (nitric oxide), which causes relaxation of vascular smooth muscle precontracted with norepinephrine, 10-8M. Removal of the endothelium by rubbing eliminates the relaxant effect and reveals contraction caused by direct action of Ach on vascular smooth muscle. (NA, noradrenaline [norepinephrine]. Numbers indicate the log concentration applied at the time indicated.)... 

NO has a significant effect on vascular smooth muscle tone and blood pressure. Numerous endothelium-dependent vasodilators, such as acetylcholine and bradykinin, act by increasing intracellular calcium levels, which induces NO synthesis (Figure 19-2). Mice with a knockout mutation in the eNOS gene display increased vascular tone and elevated mean arterial pressure, indicating that eNOS is a fundamental regulator of blood pressure. The effects of vasopressor drugs are increased by inhibition of NOS. 

These drugs act on postsynaptic acetylcholine receptors (cholinoceptors) at all the sites in the body where acetylcholine is the effective neurotransmitter. They initially stimulate and usually later block transmission. In addition, like acetylcholine, they act on the noninnervated receptors that relax vascular smooth muscle in peripheral blood vessels. 

The chemopreventive activity of hibiscus extracts has been extensively studied recently. The protective effect was demonstrated against human carcinomas, chemically induced toxicity,and hepatotoxici-jy 11,21-27 Antimutagenic activity has also been demonstrated both in vitro and in vivo The chemopreventive activity is attributed mainly to the antioxidant effect of the anthocyanins present in hibiscus extracts. Roselle decoction or infusion reportedly has hypotensive properties with no side effects. This effect has been investigated in more depth in experimental animals and in humans over the past decade and the results seem to support earlier studies especially in mild to moderate hypertension. Suggested mechanisms of action for the hypotensive activity include inhibition of Ca influx into vascular smooth muscle, NO-cGMP-relaxant pathway, and possible acetylcholine-and histamine-like vasorelaxation. ... 

The second indication came from studies of vascular regulation. Several molecules, such as acetylcholine, were known to cause relaxation of blood vessels. This effect occurred only when the vessels were prepared so that the luminal endothelial cells covering the smooth muscle of the vessel wall were retained. Subsequent studies showed that endothelial cells respond to these vasorelaxants by releasing a soluble endothelial-derived relaxing factor (EDRF). EDRF acts on vascular muscle to elicit relaxation. These findings prompted an intense search for the identity of EDRF. 

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