Acetylcholine cardiovascular effects

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. 

The cardiovascular effects of all the choline esters are similar to those of acetylcholine—the main difference being in their potency and duration of action. Because of the resistance of methacholine, carbachol, and bethanechol to acetylcholinesterase, lower doses given intravenously are sufficient to produce effects similar to those of acetylcholine, and the duration of action of these synthetic choline esters is longer. The cardiovascular effects of most of the cholinomimetic natural alkaloids and the synthetic analogs are also generally similar to those of acetylcholine. 

The most prominent pharmacologic effects of cholinesterase inhibitors are on the cardiovascular and gastrointestinal systems, the eye, and the skeletal muscle neuromuscular junction (as described in the Case Study). Because the primary action is to amplify the actions of endogenous acetylcholine, the effects are similar (but not always identical) to the effects of the direct-acting cholinomimetic agonists. 

SSRIs have less sedative, anticholinergic, and cardiovascular effects than do the tricyclic antidepressants, due to dramatically decreased binding to receptors of histamine, acetylcholine, and norepinephrine. 

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. 

A large number of prescription and nonprescription drugs, as well as a variety of plants and mushrooms, can inhibit the effects of acetylcholine at muscarinic receptors. Some drugs used for other purposes (eg, antihistamines) also have anticholinergic effects. Many of them have other potentially toxic actions. For example, antihistamines such as diphenhydramine can cause seizures tricyclic antidepressants, which have anticholinergic, quinidine-like, and a-blocking effects, can cause severe cardiovascular toxicity. 

Acetylcholine is involved in many aspects of the regulation of the cardiovascular system. Thus, it may also play a role in the control of intercellular communication. Very early in gap junction research the effect of acetylcholine as an important transmitter on gap junction conductance has been investigated. First, Petersen and Ueda [1976] demonstrated an increase in junctional resistance in pancreatic acinar cells following the application of acetylcholine. Concomitantly, the release of amylase was stimulated. A minimum concentration of 1 pmol/l acetycholine was required to evoke uncoupling. The next question was, how is the acetylcholine effect mediated Calcium has been considered to contribute to the mechanism of action [Iwatsuki and Pertersen,... 

Cardiovascular System. Atropine is sometimes used to block the effects of the vagus nerve (cranial nerve X) on the myocardium. Release of acetylcholine from vagal efferent fibers slows heart rate and the conduction of the cardiac action potential throughout the myocardium. Atropine reverses the effects of excessive vagal discharge and is used to treat the symptomatic bradycardia that may accompany myocardial infarction.4 Atropine may also be useful in treating other cardiac arrhythmias such as atrioventricular nodal block and ventricular asystole. 

Actions Carbachol has profound effects on both the cardiovascular system and the gastrointestinal system because of its ganglion-stimulating activity and may first stimulate and then depress these systems. It can cause release of epinephrine from the adrenal medulla by its nicotinic action. Locally instilled into the eye, it mimics the effects of acetylcholine, causing miosis. 

As with pilocarpine and arecoline, increased interest in pharmacotherapy of Alzheimer s disease and other memory deficit conditions has led to renewed and expanded studies of oxotremorine. This compound has little or no effect on serum or red cell but3nyl-cholinesterase. Oxotremorine has been described as a potent muscarinic partial agonist (172). However, an earlier report (11) presented evidence that oxotremorine has an indirect action in the CNS, perhaps by stimulation of choline acetyltransferase, resulting in elevation of acetylcholine levels. The peripheral actions of oxotremorine, including effects on cardiovascular mechanisms, have been ascribed (172) to preferential activation of M, receptors. Brimblecomb (211, 212) reported... 

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