Atrial Natriuretic Factor (ANF)

Researcher name: 
Adolfo J. de Bold, PhD, FRSC

In 1968, I started a project at Queen's University aimed at unravelling the function of storage granules present in the muscle of the atrial chambers of the heart. Under the microscope, these granules resemble storage granules found in cells known to produce hormones. Twelve years and innumerable investigations later, we were able to demonstrate that these granules contain a hormone (ANF) and thus, that the heart contributes to maintain blood circulation not only by its pumping action but also by producing a hormone.

Discovery, isolation, purification, determination of the chemical structure and patenting of Atrial Natriuretic Factor (ANF). This discovery established that the heart produces a hormone that helps regulate blood pressure and kidney function and paves the way for the development of new antihypertensive and diuretic drugs.

In 1968, I started a project at Queen's University aimed at unravelling the function of storage granules present in the muscle of the atrial chambers of the heart. Under the microscope, these granules resemble storage granules found in cells known to produce hormones. Twelve years and innumerable investigations later, we were able to demonstrate that these granules contain a hormone (ANF) and thus, that the heart contributes to maintain blood circulation not only by its pumping action but also by producing a hormone. The isolation and purification of this hormone is a typical example of how animals are irreplaceable in many instances. Cardiac muscle cells (like nerve cells) do not multiply in culture so that one is forced to use fresh animal tissues to obtain enough of the material to be characterized. Because the hormone is present in very small quantities, many rat hearts were used to develop an isolation method for ANF. As described below, the findings more than justified the effort, which started as a curiosity.

The newly discovered hormone was named Atrial Natriuretic Factor because it was discovered by virtue of its property of inducing the kidneys to excrete increased amounts of sodium in the urine (natriuresis) and its tissue source was the heart atria. The new field of research grew from just one article describing its discovery in 1981 to almost 6,000 articles in today's biomedical literature. The reason for this phenomenal interest in ANF stems from two facts: 1. The concept that the heart produces a hormone was totally unprecedented; 2. ANF can exert a large number of biological effects. Conceptually, ANF may be viewed as a hormone that is released from the upper two chambers of the heart – the atria – when extra blood volume is detected through the stretch induced in these chambers. If this extra load is detected over relatively long periods of time as, for example, in some disease states, the heart increases not only the rate of release of this hormone but also its rate of production. The varied effects makes ANF of interest to the basic scientist as well as to the clinical scientist and the pharmaceutical industry. The latter is trying to develop drugs that will mimic the effects of ANF, including its safe diuretic and blood pressure lowering effects. A drug with such properties could have a multimillion dollar market and can benefit millions of people yearly.

The ANF discovery is one of the best examples of how a basic science fact was turned into a finding of immense significance for the pharmaceutical industry and the better understanding of disease.

The above work was supported by the Heart and Stroke Foundation of Ontario and the Medical Research Council of Canada and succeeded despite the efforts of many skeptics who considered that research should be targeted.