Vasodilator autacoids

Acetylcholine is the neurotransmitter at all these sites, acting on a postsynaptic receptor, except on most blood vessels in which the action of cholinergic drugs is unrelated to cholinergic vasodilator nerves. It is also produced in tissues unrelated to nerve endings, e.g. placenta and ciliated epithelial cells, where it acts as a local hormone (autacoid) on local receptors. 

In fact, a medley of substances (autacoids), kinins, prostaglandins, leukotrienes, histamine, endorphins, serotonin, vasopressin, has been implicated. In endotoxic shock, the toxin also induces synthesis of nitric oxide, the endogenous vasodilator, in several types of cells other than the endothelial cells which are normally its main source. 

As an autacoid, adenosine possesses negative chronotropic and inotropic effects, is a vasodilator in almost all vascnlar beds, inhibits nenrotransmitter release in the CNS, canses sedation, displays anticonvnlsant activity, regulates renin release, inhibits platelet aggregation, modulates lymphocyte function, induces bronchospasm, and inhibits hpolysis. 

As autacoids, bradykinin and kallidin increase vascular permeability, produce vasodilation, increase the synthesis of prostaglandins, and cause edema and pain. Extensive evidence exists that bradykinin and other kallidin substances contribute to the pathogenesis of the inflammatory response that occurs in acute and chronic diseases including allergic reactions, arthritis, asthma, sepsis, viral rhinitis, and inflammatory bowel diseases (see Figure 30). 

A number of factors, including tissue damage, allergic reactions, viral infections, and other inflammatory events, activate a series of proteolytic reactions that generate bradykinin and kallidin in tissues. These peptides contribute to inflammatory responses as autacoids that act locally to produce pain, vasodilation, and increased vascular permeability. Much of their activity is due to stimulation of the release of potent mediators such as prostaglandins, NO, or endothelium-derived hyperpolarizing factor (EDHF). 

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