Positive inotropic substances

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

Cardiotonic agents are sometimes called positive inotropic drags, i.e. substances that enhance the strength of muscle contractions, and in this case those that enhance the strength of myocardium contraction. Cardiotonic drugs are intended for treating cardiac insufficiency. 

C22H34O7, Mr 410.51, cryst., mp. 230-232 °C, [a]u -26.2 (CHCI3). Cardioactive diterpenoid (" labdane type) from the Indian medicinal plant Coleusforskolii (Lamiaceae). F. has a positive inotropic effect, it lowers blood pressure and has general vasodilatatory activity, especially on intravenous administration. The activity results from a direct stimulation of adenylate cyclase. F. is the archetype for all substances with this mechanism of action. In laboratory experiments it has been used successfully in therapy of congestive cardiomyopathy, glaucoma, or asthma. Several F. derivatives with improved solubility in water have been prepared. ... 

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