Generally ETa receptors are considered important in effecting contraction and mitogenic effects on smooth muscle cells and fibroblasts. However, in human arteries, the small resistance arteries appear to have contraction-inducing ETb receptors. There are a number of potential ETa and ETb receptor antagonists that block hypoxic vasoconstriction. These agents potentially offer the next therapy to be introduced in the treatment of pulmonary hypertension. Clinical trials are awaited.
Indirect Measures for Pulmonary Endothelium Dysfunction: We have seen that measures of urinary excretion of PGI2 and thromboxane A2, exhaled rates of NO, and plasma levels of ET-1 are all altered in pulmonary hypertension, and as such could provide useful markers of the pathologic process.
A further measurement requires investigation. Herve and colleagues described a patient with PPH with an inherited platelet pool storage defect. Canadian neighborhood pharmacy Here This patient had elevated serotonin levels in the plasma. This group reported PPH patients with reduced platelet but increased plasma levels of serotonin that remained abnormal after lung transplantation.
A similar pattern of abnormal platelet storage of serotonin is observed in the Fawn-hooded rat that has a susceptibility to developing pulmonary hypertension when exposed to mild hypoxia. Indeed, this strain excessively expresses ET-1. To further heighten interest in serotonin and platelets, the anoretic drug dexfenfluramine has been associated with a significant risk of developing PPH. This agent induces a similar leakage of serotonin from platelet stores as that inherent in the Fawn-hooded rat. The link between circulating plasma and platelet levels of serotonin is tentative at the moment in PPH patients and requires further study. However, a case could also be made for measuring the circulating levels of serotonin in platelets and plasma to assess risk.