Aging Begins at 30

A Word About Peptides

Every now and then a new discovery considerably widens the horizon of possible benefit to humankind. Someone theorized in 1980 that increased blood volume in some patients with heart disease or high blood pressure might stretch the weakest component in the vascular system and the body might register a protest in the blood. Such a weak spot is the entrance hall (called an atrium in Greek) to the heart pumps (ventricles). This led to intravenous injection of an extract of rat atrial tissue in rats. A copious natriuresis, or loss of sodium and water, resulted. (Natrium for sodium and oesis for water making.) So the first member of a family of peptides was found. Peptides are chains of amino acids. As well as these effects the peptides relaxed blood vessels and protected the rat body against raised blood pressure and increased blood volume.

Three peptides share 17 amino acids with different head and tail amino acids attached. They are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) under varying hormone or neurotransmitter control. Their effect varies according to where there is a docking (receptor) site. They then trigger cGMP controlled signals. Their action ends when endopeptidases (aminoacid clippers) in the kidney or blood vessels inactivate them. Some act directly on the brain to decrease salt appetite and water drinking. They also subdue signals from the sympathetic nervous system and inhibit deleterious overgrowth of damaged heart muscle. Similar peptides in the gastrointestinal tract regulate salt and water transport across the gut wall.

The natriuretic peptides therefore defend the body against excess salt and water retention. Patients with congestive heart failure, that is swollen edematous legs and severe shortness of breath, have high circulating levels of ANP and BNP; as much as 30 times normal. These high levels predispose them to abnormal heart rhythms and a poor survival outlook. Later in severe failure the levels fall as the circulation in the kidney fails. Something similar happens in the blood volume overload of kidney failure.

Oral inhibitors (antagonists) to these peptides have been used in heart failure. In high blood pressure studies in rats those with 10-fold increases in natriuretic peptides have 20 - 30 mm Hg lower blood pressures. These peptides defend against salt or mineralocorticoid (aldosterone) induced high blood pressure. So far their effects on human high blood pressure await study but the prospects are encouraging.

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