Cardiovascular disease is one of the leading deaths in the United States. Pulmonary hypertension disease one type of cardiovascular disease that is due to the narrowing of the arteries within the lungs. When the arteries are narrowed the right side of the heart is unable to pump blood through the lungs, pressure begin to build up and not enough oxygen is being picked up, therefore causing pulmonary hypertension. If there are damages to the endothelium, it can cause this disease because it can produce more endothelin-1, which is one of the isomer of Endothelin that influence as a vasoconstrictor.
It is important to have treatment available to patients who suffer from cardiovascular diseases. Since it is one of the leading causes of deaths in the United States, improving treatments will save many lives. Although heart disease occur more in adult patients, there are possible chances in which infants are affected by a disease known as the congenital heart disease. In order to have treatment for patient with heart disease, we need to look at the molecular level. Patients were examined and documents showed that endothelial injury may be the cause for pulmonary hypertension and other vascular diseases.
Endothelin is a 21 amino acid polypeptide that has 3 different isoforms which are endothelin-1(ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). ET-1 is located mainly in the endothelial cell but is a regulator of smooth muscle, heart, and kidney. ET-2 differs from ET-1 by 2 amino acids and is also found in the heart and kidney. ET-3 differs from ET-1 by 6 amino acids and is produced in the central nervous system like ET-1and in gastrointestinal (1). With researches, ET-1 is more focused on in cardiovascular diseases because it is a vasoconstrictor, which is the narrowing of the blood vessels that causes such heart diseases.
In humans, the endothelin-1 is converted to another form which is the preproendothelin-1 and then cleaved into proendothelin and then forming into its functional form by an enzyme called the endothelin converting enzyme-1 (1). There are two receptors that intercede with the endothelin protein which are ETA and ETB receptors. ETA receptors are on the vascular smooth muscle, while ETB receptors are located on the endothelial cells. When ETA receptor is stimulated by endothelin-1, it becomes responsible for the constriction of the vascular smooth muscle. ETB receptor is different in that it provokes the production of nitric oxide. The alterations of these two receptors may cause cardiovascular effects.
To understand how ETA and ETB receptors work, antagonist receptors were introduced in humans. ETA receptor antagonist cause slow vasodilation, which is the widening of the blood vessels. This decrease the blood pressure, which means that endothelin-1 that reconcile with ETA receptor cause vasoconstriction. When ETB receptor antagonist was introduced, it causes vasoconstriction and also blocks other...