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Prostacyclin analogs have been shown to be effective in the treatment of pulmonary hypertension. Multiple for-mulations are now available including intravenous, inha-lational, and more recently, oral. These agents activate the G protein-coupled IP receptor, leading to elevated cAMP. The result is reduced proliferation of vascular smooth mus-cle cells and vasodilation, key strategies in the treatment of pulmonary hypertension.
Samie R. Jaffrey, MD, PhD
Nitric oxide (NO) is a gaseous signaling molecule that readily diffuses across cell membranes and regulates a wide range of physiologic and pathophysiologic processes including cardiovascular, inflammatory, and neuronal functions. Nitric oxide should not be confused with nitrous oxide (N2O), an anesthetic gas, or with nitrogen dioxide (NO2), a toxic pulmonary irritant gas.
The understanding that NO is an endogenously synthesized signaling molecule came from a series of discoveries that began with Italian chemist Ascanio Sobrero, who synthesized nitroglycerin in 1846 and found it to be unstable and explosive. Nevertheless, upon tasting the chemical, which was not an unusual practice at the time, he noted profound headache, which was soon understood to be caused by cerebral vasodilation. Based on this early observation, nitroglycerin was used to treat angina and hypertension within 20 years.
These and other early studies demonstrated that human cells have the capacity to detect and respond to nitroglycerin, as well as its metabolite, NO. However, the first indication that there may be an endogenous source of NO came from studies of cultured macrophages, which release byproducts of NO breakdown, including nitrate and nitrite, after treatment with inflammatory mediators such as bacterial endotoxin. Similarly, injection of endotoxin in animals elevated urinary nitrite and nitrate.