Circulatory diseases can be treated more effectively today than in the nineteenth century because we understand a lot about how blood circulates and what controls the dynamics of that circulation. There was a time, however, when the very idea of circulation was not accepted. In the second century the Greek anatomist Galen declared correctly that arteries carry blood, not air, but he left behind some stunning misconceptions in other areas, suggesting, for example, that the liver was the center of the blood system. Many of those errors were swept away by De Motu Cordis (On the Motions of the Heart), a seminal work by William Harvey published in 1628. "Just as the king is the first and highest authority in the state," Harvey declared, "so the heart governs the whole body!"

An even greater contribution of De Motu Cordis, however, was Harvey's insight that blood circulates. To determine the direction of blood movement to and from the heart, Harvey dissected and tied off blood vessels. He concluded that a huge volume of blood moves away from the heart and into the tissues. This quantity of blood could not possibly be created anew at the heart or disappear as food in the tissues. Rather, the blood must flow to the tissues and then return to the heart in a continuous cycle.

A century later, Stephen Hales, a curate in the English country town of Teddington, realized that Harvey's steady cycle of circulating blood actually varied over time. In a series of experiments with horses, a sheep, a doe, and an assortment of dogs, Hales defined the concept of blood pressure. His central experiment, published in 1733, involved tying down a mare, inserting a narrow brass pipe into an artery, and fitting a 9-foot-long vertical glass tube to the pipe. The pressure of the horse's circulation forced the blood up the glass tube to a height of 8 feet, 3 inches. With the beating (rapid, we presume) of the horse's heart, the blood rose and fell by 2 to 4 inches. Hales recognized that the peak pressure reflected the exertions of the contracting heart, and that the low pressure was a measure of how much the blood vessels throughout the body resisted blood flow.

Hales also found that removing blood from the animals caused their blood pressure to drop. However, this was not the only way to affect blood pressure. A few years earlier, in 1727, a French physiologist named Pourfois du Petit had reported that cutting a nerve at the neck caused a blood vessel in the eye to dilate; other experiments demonstrating constriction of blood vessels followed. By the early 1800s anatomists had figured out that the smooth muscles surrounding blood vessels contracted or relaxed in response to signals from various nerves, thereby squeezing the blood vessels or allowing them to dilate.

Measuring blood pressure became practical as Hales's brass and glass contraption was gradually refined during the nineteenth century. In 1854, the physiologist Karl von Vierordt of Tübingen, Germany, realized that the same assessment could be made by measuring how much external pressure was needed to stop blood flow. Vierordt came up with a cumbersome system of weights and levers that eventually led to the idea of the blood pressure cuff. After several improvements, the modern version of this device debuted in 1905, enabling physicians to correlate blood vessel dilation with lowered blood pressure. Clearly, the body maintained exquisite control over blood pressure, and it did so at least partly through the nerves, but the details of this process remained hidden.