Cardiovascular peptides
Many vasoactive peptides are implicated in vascular (patho)biology. Of particular importance are those identified as therapeutic targets in cardiovascular disease (CVD): angiotensin II (Ang II), endothelin (ET-1, and ET-2), and natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide), which all act via specific G protein-coupled receptors. Serotonin also has vasoactive activity and is a therapeutic target in CVD, but will not be discussed in depth in this topic. ET, Ang II and serotonin are primarily vasoconstrictors with growth-promoting activity, whilst the natriuretic peptides are vasodilators which promote urinary excretion of sodium ions (natriuresis).
Ang II raises blood pressure primarily by causing vasoconstriction and increasing aldosterone secretion in the kidney. Ang II also promotes growth, cell migration, and mitosis of vascular smooth muscle cells, and increases fibrotic thickening of the vascular wall and mtocardium. Ang II actions are mediated via the angiotensin II receptor type 1 (AT1). Losartan, candesartan, irbesartan, valsartan, eprosartan, telmisartan, and olmesartan are AT1 antagonists used as anti-hypertensives (further details provided in the Angiotensin receptor antagonists topic of the Cardiovascular drugs section of this resource).
Endothelins act through activation of endothelin receptors, ETA and ETB. Endothelin receptor antagonists macitentan, bosentan and ambrisentan are used to treat pulmonary arterial hypertension (PAH). Macitentan and bosentan antagonise both ETA and ETB; ambrisentan is selective for ETA. Endothelin receptor antagonists should not be prescribed to anaemic patients.
Atrial natriuretic peptide (ANP) is secreted from myoendocrine cells in response to high blood volume and has the opposite effect to renally produced aldosterone on sodium in the kidneys: ANP generates sodium loss; aldosterone stimulates sodium retention. ANP is metabolised by the enzyme neutral endopeptidase (NEP, or neprilysin), with NEP inhibitors being investigated as potential therapeutics for congestive heart disease and hypertension.