Therapeutic potential of endothelin receptor antagonists and nitric oxide donors in pulmonary hypertension.
Pulmonary hypertension can occur idiopathically as a primary disorder of the pulmonary circulation or more commonly, it can exist as a haemodynamic manifestation of a wide variety of pulmonary and cardiovascular diseases, including acute lung injury, chronic obstructive lung disease, congenital heart disease, mitral stenosis, chronic left-sided congestive heart failure and connective tissue diseases such as scleroderma. Pulmonary hypertension is associated with changes in vascular tone as well as vascular structure, with the relative contribution of each dependent upon the aetiology of the increased pulmonary vascular resistance. Most currently available treatments utilise anticoagulants as well as vasodilator drugs that only attenuate the vasoconstrictive component of the disease. The latter category includes oral calcium channel blockers, iv. and aerosolised prostacyclin analogues and inhaled nitric oxide but all three classes of vasodilators have disadvantages and limitations. Treatment with vasodilators is often ineffective in patients with longstanding pulmonary hypertension in which structural changes contribute significantly to the pulmonary hypertension, blood flow obstruction and right heart failure. In view of the immense clinical need, new therapies are being developed by pharmaceutical companies to treat pulmonary hypertension. This update will focus on the current development status of endothelin receptor antagonists and nitric oxide donors for the treatment of pulmonary hypertension.
Tilton
R G
RG
Department of Pharmacology, Texas Biotechnology Corporation, Houston, Texas, TX 77030, USA. rtilton@tbc.com
Brock
T A
TA
Dixon
R A
RA
D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D020030:Nitric Oxide Donors; D009569:Nitric Oxide