Acetylcholine vasodilator effect

Acetylchohne is a vasodilator that acts by causing relaxation of the smooth muscle of blood vessels. However, it does not act directly on smooth muscle. A key observation was that if endothefial cells were stripped away from underlying smooth muscle cells, acetylcholine no longer exerted its vasodilator effect. This finding indicated that vasodilators such as acetylcholine initially interact with the endothelial cells of small blood vessels via receptors. The receptors are coupled to the phos-phoinositide cycle, leading to the intracellular release of... 

The vasodilating effect of papaverine and acetylcholine on the renal function has been described (297-301). Harsing et al. (297) found that... 

Royal jelly exhibited a transient vasodilating effect on dog femoral artery, which was due to its acetylcholine constituent. Peptides present in royal jelly were found to possess antihypertensive effect when orally administered in hypertensive rats for 28 days. A similar effect was observed in rats administered a royal jelly protein hydrolysate, and the antihypertensive effect was attributed to the inhibition of ACE. " ... 

The primary cardiovascular effects of muscarinic agonists are reduction in peripheral vascular resistance and changes in heart rate. The direct effects listed in Table 7-3 are modified by important homeostatic reflexes, as described in Chapter 6 and depicted in Figure 6-7. Intravenous infusions of minimally effective doses of acetylcholine in humans (eg, 20-50 mcg/min) cause vasodilation, resulting in a reduction in blood pressure, often accompanied by a reflex increase in heart rate. Larger doses of acetylcholine produce bradycardia and decrease atrioventricular node conduction velocity in addition to hypotension. 

VIP exerts significant effects on the cardiovascular system. It produces marked vasodilation in most vascular beds and in this regard is more potent on a molar basis than acetylcholine. In the heart, VIP causes coronary vasodilation and exerts positive inotropic and chronotropic effects. It may thus participate in the regulation of coronary blood flow, cardiac contraction, and heart rate. 

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. 

Receptor-dependent vasodilation may also take place in a more indirect manner through the presynaptic modulation of the release of neurotransmitters, such as norepinephrine and acetylcholine. In addition to its effects on postsynaptic receptors, norepinephrine stimulates the presynaptic a2-receptor, thereby inhibiting further transmitter release. Moreover, the activation of other presynaptic receptors such as the muscarinic cholinergic, dopaminergic, purinergic, serotoninergic, and histaminergic receptors leads to diminished norepinephrine release and subsequent vasodilation. 

A number of vasodilators, such as acetylcholine, bradykinin, adenine nucleosides, thrombin, histamine, and serotonin, require an intact vascular endothelium to exert their effects. For example, stimulation of endothelial cholinergic receptors causes the release of endothelium-derived relaxing... 

Due to the adverse effects associated with the therapies described, many investigators advocate testing for pulmonary vascular responsiveness. The potential for reversal of pulmonary vascular resistance is assessed either by a selective pulmonary vasodilator such as acetylcholine or by a short-acting, easily titratable, nonselective vasodilator such as prostacyclin. These agents appear to be more predictive of pulmonary vascular responsiveness than administration of 100% oxygen or intravenous phenotolamine. Rozkovec et al. (1982) suggest that patients who have a greater than 20% fall in total... 

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