Endothelial Dysfunction Providing the Basis for the Treatment of Pulmonary Hypertension: Nitric Oxide

7 Jun

In PPH patients at rest, the relative release of thromboxane A2 compared with PGI2 is greater than normal. This observation in PPH patients may be explained by the relatively poor expression of the PGI2 synthase transcript and protein in their pulmonary vasculature (N. Voelkel, MD; personal communication; 1997).
The use of continuous infusions of PGI2 in PPH patients does not simply offer patients a vasodilatation, but may also restore the imbalance between thromboxane A2 and PGI2 release. There is evidence that the ability of the treatment to improve survival is not associated with its ability to achieve pulmonary vasodilatation (Fig l).
Nitric Oxide
Inhaled NO: A Treatment for Pulmonary Hypertension: Following the discovery of endothelium-derived relaxing factor by Furchgott, it was positively identified as the gas, NO. The enzyme, nitric oxide synthase (NOS), was later described that elaborates the gas from molecular oxygen and L-arginine. Three isoforms are recognized: NOS I found in most cells but first identified in nerves; NOS II also found in most cells and previously known as inducible or iNOS; finally NOS III found in endothelial cells.
Although NO donor molecules such as glyceryl trinitrite have been used therapeutically since the 19th century, since NO is a gas, it was difficult to consider it as a direct treatment. However, inhaled NO had been used previously as a means of measuring lung diffusion capacity alongside carbon monoxide Here canadian family pharmacy online. As with carbon monoxide, NO is relatively insoluble in water but has a high affinity for hemoglobin; when inhaled at 80 ppm NO, almost 95% is retained within a 7-s breath-hold This suggests that it could reach the precapillary arteries, known to be associated with alveoli and situated within a very short diffusion distance.
NO acts principally on the haem moiety of the enzyme guanylate cyclase to cause activation with the resulting rise in cyclic guanosine monophosphate producing smooth muscle relaxation It was, therefore, likely that inhaled.

Figure 1. Percentage survival of (top, A) those patients who had pulmonary vasodilation (measured as a fall in mean pulmonary artery pressure) with epoprostenol and (bottom, B) those patients who had no vasodilation with epoprostenol.

Figure 1. Percentage survival of (top, A) those patients who had pulmonary vasodilation (measured as a fall in mean pulmonary artery pressure) with epoprostenol and (bottom, B) those patients who had no vasodilation with epoprostenol.