Vascular Action

Cocaine produces vasoconstriction (blanching) probably by sensitizing to sympathetic stimulation. This action is lacking in the other local anesthetics. Procaine has practically no vascular effect alypin, eucaine, and stovaine cause some dilatation. Cocaine decreases capillary hemorrhage procaine, apothesine, and other synthetic anesthetics tend rather to increase bleeding. 

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Raymond-Hamet has made a special study of the vascular action of the harmala alkaloids and certain of their proximate derivatives, including their influence on the pressor and other effects of adrenaline in comparison with that of yobyrine and ketoyobyrine (pp. 505-6). 

NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

Finally, purines such as caffeine (including dietary caffeine in coffee, tea, colas, and chocolate) and synthetic derivatives, such as theophylline, can interfere with the vascular actions of dipyridamole, These agents act to inhibit the adenosine A2A receptor, which serves to further emphasize the role of adenosine in the pharmacologic actions of dipyridamole (41-43), It has also been shown that this effect on A2A receptors is restricted to the vessel wall the direct anti-aggregatory actions of dipyridamole are not blocked by purines and may, if anything, be enhanced by the indirect effect of purines to upregulate A2A receptors (44,45). 

Cocaine also blocks the reuptake of norepinephrine in the PNS the combination of central and peripheral actions leads to a high probability of toxicity. The cardiovascular system is particularly sensitive to the actions of cocaine, and cardiac arrhythmias, marked increases in blood pressure, cerebral hemorrhage, myocardial ischemia, and outright heart failure are not uncommon with cocaine use. Even young, otherwise healthy individuals with normal coronary and cerebral arteries have died suddenly after cocaine use from cerebral hemorrhage or ventricular fibrillation. There have been several deaths of famous athletes attributed to cocaine cardiotoxicity. These cardiotoxic effects may be related to increased intracellular calcium levels and involve both cardiac and vascular actions of the drug. 

Due to the dual renal and vascular action of AVP, scientists at Yamanouchi Pharmaceuticals became interested in the identification of dual Vla/V2 vasopressin receptor antagonists, particularly because such agents were anticipated to be of unique utility in the treatment of congestive heart failure (CHF), where aberrant AVP secretion appeared responsible for both the onset of hypervolemic hyponatremia and deleterious increases in vascular resistance.14 The resulting drug discovery program ultimately lead to the identification of conivaptan HCl (1). 

Spokas E G, Folco G, Quilley J et al 1983 Endothelial mechanism in the vascular action of hydralazine. Hypertension 5 1107-1111... 

Olson KR. 2005. Vascular actions of hydrogen sulfide in nonmammalian vertebrates. Antiox Redox Signal 7 804-812. O Reilly JP, Cummins TR, Haddad GG. 1997. Oxygen depri-... 

Genazzani, E., and L. Sorrentino. 1962. Vascular action of acteina Active constituent ol Actaea racemosa L. Nature 194 544-555. 

The present study critically re-examines the mechanism of kinin release and explores the vascular action of kinin in the presence of other chemical mediators. 

The data indicate that the ordinary vascular action of both kinin and histamine can be altered or reversed when these mediators are present together. This agrees broadly with previous reports on the interaction between these two mediators relative... 

Piomelli D, Pinto A, Tota B. Divergence in vascular actions of prostacyclin during vertebrate evolution. J Experim Zool 1985 233 127-131. 

Diazoxide - An Jji vitro pharmacodynamic study was de-signed to specify the type(s) of inhibition involved in the vascular action of diazoxide. The results indicate that diaz> oxide competes with barium for a specific receptor site in the vascular smooth muscle of the rat aorta. The location of this receptor is apparently closer to the process of muscle contraction than the a-adrenergic receptor, and may be a site normally activated by calcium. The specific competitive inhibition of barium-stimulated vasoconstriction by diazoxide may help to explain the mechanism by which diazoxide, and possibly other benzothiadiazine antihypertensive agents, reduce blood pressure. ... 

Okamoto, S., Handa, H., Toda, N., 1984 Role of intrinsic arachidonate metabolites in the vascular action of erythrocyte breakdown products. Stroke 15, 60 4. 

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