Archive for the ‘Hypertension’ Category

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 […]

To explain this apparent lack of specificity of expression of ET-1 requires further understanding of the regulation of ET-1 production. Circulating levels of ET-1 are elevated in patients with hypoxic lung disease and, of interest, on ascent to altitude, the plasma ET-1 levels rise in association with the fall in arterial partial pressure of oxygen. […]

Experimentally, in isolated pig lungs, we have demonstrated that the exhaled NO level falls when L-NAME is added to the perfusate and that ACh increases and hypoxia reduces exhaled NO in this preparation. The pulmonary vascular resistance rose and fell with the NO level. These results and those of other workers suggest that the pulmonary […]

NO would cause pulmonary vasodilatation. Indeed, we were able to prove that this was the case in 1988. In patients with pulmonary hypertension, inhaled NO (unlike IV PGI2) acted as a selective pulmonary vasodilator (Fig 2). Others quickly showed the same response in patients with ARDS and neonatal PPH. Indeed, inhaled NO has been shown […]

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 […]

Impaired Release of PGI2 in Pulmonary Hypertension: Arachidonic acid is released from cell membrane phospholipids by the action of phospholipase A2 and C. In endothelial cells and platelets, these enzymes are activated by a number of stimuli, including thrombin, epinephrine, and sheer stress. A two-step oxygenase, eyclo-oxygenase, converts arachidonic acid to prostaglandin H2 or endoperoxide. The constitutive form of […]

This review will consider prostacyclin (PGI2), nitric oxide (NO), and endothelin-1 (ET-1). It will also introduce an important interaction between platelets and the endothelium in lung disease. The aim is first, to provide an indication for treatment based on endothelial dysfunction and second, to identify methods of noninvasive measurement that might be used to assess […]