Vasodilators indirectly acting

Digoxin remains the mainstay of treatment for patients with chronic myocardial failure. Other drugs with inotropic and/or vasodilator properties, including the catecholamines and phosphodiesterase III (PDE) inhibitors, are used in the treatment of acute cardiac failure. The inotropic actions of most of these drugs result from a direct or indirect elevation of [Ca2-i-]i (intracellular Ca2+ concentration). This acts as a trigger for a process which leads to increased contractile state and cardiac contraction (Figures 8.3 and 8.4). Myofilament calcium sensitisers increase the sensitivity of contractile proteins to calcium. Some newer drugs, such as vesnarinone, have multiple mechanisms of action. 

Cilostazol has a number of additional indirect effects. Similar to dipyridamole, it enhances the actions of prostacyclin, although it has not been reported to directly increase prostacyclin release, Cilostazol also affects endothelial cells, specifically the release of cytokines, such as monocytic chemoattractant protein-1 (MCP-1), which appears to play an important role in the development and progression of atherosclerotic lesions (24). Cilostazol, like other PDE3 inhibitors, acts as a vasodilator. 

Carbon dioxide is a rapid, potent stimulus to ventilation. Inhalation of 10% CO can produce minute volumes of 75 L/min in normal individuals. Carbon dioxide acts at multiple sites to stimulate ventilation. Elevated Pco causes bronchodilation, whereas hypocarbia causes constriction of airway smooth muscle these responses may play a role in matching pulmonary ventilation and perfusion. Circulatory effects of CO result from the combination of direct local effects and centrally mediated effects on the autonomic nervous system. The direct effects are diminished contractility of the heart and vascular smooth muscle (vasodilation). The indirect effects result from the capacity of CO to activate the sympathetic nervous system these indirect effects generally oppose the local effects ofCO. Thus, the balance of opposing local and sympathetic effects determines the total circulatory response to CO. The net effect of CO inhalation is an increase in cardiac output, heart rate, and blood pressure. In blood vessels, however, the direct vasodilating actions of carbon dioxide appear more important, and total peripheral resistance decreases when the Pco is increased CO also is a potent coronary vasodilator. Cardiac arrhythmias associated with increased Pco are due to the release of catecholamines. 

Pancreatic secretion is controlled neurologically and hormonally. When food is given to a dog whose stomach has been disconnected from the duodenum and directly connected to the skin of the abdomen, and a pancreatic fistula is produced, the act of eating stimulates the secretion of pancreatic juice. Vagotomy suppresses this effect. Direct stimulation of the vagus also stimulates pancreatic secretion. In addition stimulation of the sympathetic system influences pancreatic secretion, but this is more likely an indirect effect of vasodilation of the gland and the musculature of the... 

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