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Pulmonary Hypertension: A Case Study

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PAH is a diseases of vascular tissue of the pulmonary system. The disease progresses rapidly. It is defined hemodynamically as a mean arterial pressure (mPAP) > 25 mmHg and pulmonary capillary wedge pressure (PCWP) of < 15 mm Hg. PAH is characterized by destructive vascular changes that include: inflammation, vasoconstriction, cell proliferation, hypertrophy and (in severely symptomatic patients) formation of plexiform lesions (Archer, Weir & Wilkins, 2010). Progression of these structural changes eventually leads to right ventricular strain and dysfunction.
Within the pulmonary vasculature, three pathways that are known to be involved in pulmonary arterial hypertension include: endothelin, nitric oxide and prostacyclin. These pathways …show more content…
In normal physiology, circulating endothelin helps maintain normal vascular tone. In PAH, levels are elevated in the blood stream and the capacity to clear endothelin from the circulation is reduced. Endothelin exerts its effects by activating two distinct receptors, endothelin A (ETA) and endothelin B (ETB) (Archer et al., 2010). These receptors mediate the pathophysiologic role of endothelin in PAH. In normal physiology, endothelial cells express only the ETB receptor and smooth muscle cells express both receptors. ETA receptors on smooth muscle cells primarily mediate vasoconstriction and cellular proliferation. In PAH, excessive stimulation of ETA receptors is thought to cause vasoconstriction, cell proliferation and hypertrophy (Archer et al., 2010). ETB receptors, located on the endothelial cells, mediate endothelin dependent vasodilation. On smooth muscle cells these receptors mediate vasoconstriction. It is hypothesized that under pathologic conditions, smooth muscle cell vasoconstriction predominates due to down regulation of ETB on endothelial cells and up regulation on smooth muscle cells and the vasodilating response decreases and the vasoconstrictive response …show more content…
Nitric oxide is a vasodilator that also inhibits platelet aggregation, thrombosis and inflammation. Under normal conditions, nitric oxide is produced continuously in the vascular endothelium. Nitric oxide diffuses into vascular smooth muscle cells where it binds to and activates guanylate cyclase stimulating the synthesis of cGMP, a second messenger for signaling smooth muscle relaxation and inhibiting cellular proliferation (Archer et al., 2010). Rising levels of cGMP mediate the effects of nitric oxide. In PAH, levels of nitric oxide synthase are decreased, promoting vasoconstriction and cellular proliferation in vascular smooth muscle cells (Pietra et al., 1989). The availability of nitric oxide is also affected by the phosphodiesterase type-5 (PDE-5) enzyme, which degrades cGMP in vascular smooth muscle cells and counteracts the vasodilator effects set in motion by nitric oxide. Inhibition of PDE-5 can block this break down of cGMP (Pietra et al.,

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