Prostacyclin vascular tone

A thrombotic tendency is present in diabetes due to an imbalance between prostacyclin and thromboxane. Lipid peroxides and newly generated free radicals are thought to inhibit the vasodilator and anti-platelet effects of endothelial-derived prostacyclin, but stimulate platelet cyclooxygenase activity, thereby promoting the production of thromboxane A2. This leads to vasoconstriction and platelet aggregation - the concept of peroxide vascular tone (Halliwell and Gutteridge, 1989). 

The endothelium has many diverse functions that enable it to participate in in-flammatoiy reactions (H27). These include modulation of vascular tone, and hence control of local blood flow changes in structure that allow leakage of fluids and plasma proteins into extravascular tissues local accumulation and subsequent extravasation into tissues of leukocytes and synthesis of surface molecules and soluble factors involved in leukocyte activation (B43). The endothelial cells themselves can modulate vascular tone by the release of vasoactive substances such as prostacyclin, nitric oxide (NO), ET. Endothelium-derived vasoactive substances... 

Fig. 29.11. The effects of endothelin-1, prostacyclin and nitric oxide on the contraction and relaxation (vasodilation) of vascular smooth muscle cells. (From Yeh DC, Michel T. Pharmacology of Vascular Tone. In Golan DE, Tashjian AH, Armstrong E, et al.. Principles of Pharmacology The Pathophysiologic Basis of Drug Therapy. Baltimore Lippincott Williams Wilkins, 2004 with permission)...

The regulation of the vascular tone by the endothelium is due predominantly to the endothelial formation of several potent vasorelaxing factors involving nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (PGI2) (Fig. 76.1). 

The involvement of prostanoids in the vascular system spans from their involvement in platelet aggregation, hemostasis and thrombosis, to the regulation of the vascular tone and mediation of many vascular pathologies. One pair of prostanoids, TXA, and prostacyclin (PGI ), play an essential role in... 

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. 

Vascular endothelium and smooth muscle play important roles in regulating blood vessel tone and BP. These regulating functions are mediated through vasoactive substances that are synthesized by endothelial cells. It has been postulated that a deficiency in the local synthesis of vasodilating substances (e.g., prostacyclin and bradykinin) or excess vasoconstricting substances (e.g., angiotensin II and endothelin I) contribute to essential hypertension, atherosclerosis, and other diseases. 

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