How blood pressure is regulated

Some appreciation of the complex ways in which blood pressure is controlled may be helpful in understanding how the different classes of blood pressure lowering medications work. A useful analogy for understanding the basics of blood pressure regulation is a garden hose. The water pressure can be increased in two ways- either by opening the faucet and pumping more water through, or by tightening the nozzle and increasing the resistance to the outflow of water. In exactly the same way, the blood pressure is dependent on two factors, the amount of blood being pumped by the heart (the cardiac output) and the resistance to flow (the peripheral resistance). The latter is regulated largely by the caliber of the small arteries (arterioles), which have muscle fibers in their walls, and like the nozzle on the garden hose can constrict and dilate. This means that when your blood pressure goes up it can do so in three ways, either by an increase in the cardiac output or by constriction of the arterioles, or by a combination of the two. When you exercise, your pressure goes up because of an increased cardiac output, because the muscles need a greater flow of blood. If you put your hand in iced water your pressure also goes up, but in this case it's purely from constriction of the arterioles.
The brain plays a major role in the regulation of the circulation, through two sets of nerves, which act as the yin and yang of circulatory control. One, the sympathetic nervous system, causes the heart to speed up, while the other, the parasympathetic system, makes it slow down. This dual control system allows for very fine-tuning of the heart. Both systems are normally switched on: when our heart rate starts to go up at the beginning of exercise it does so by a combination of decreased parasympathetic and increased sympathetic nerve activity. The parasympathetic nerves are mainly involved in the regulation of the heart, while the sympathetic nervous system also controls the tone of the blood vessels, and mediates the 'fight and flight response' characterized by an increased cardiac output and blood pressure. This is something we all recognize, and is experienced as pounding of the heart, sweating, and anxiety. In evolutionary terms this was the appropriate preparation for vigorous physical exercise, whether it be fighting or fleeing from a foe. In modern times our threats are more often psychological rather than physical, and this pattern of response may be less appropriate for dealing with them.
The sympathetic nerves transmit their message to the muscle cells of the heart and arteries by releasing a chemical called norepinephrine from the nerve terminals, which rest on the surface of the muscle cells of the heart and arterioles. The norepinephrine molecules latch on to specific receptor sites on the membrane of the muscle cells, which then send a chemical signal to the inside of the cell to initiate the process of contraction. These receptors are called adrenergic receptors (in Europe norepinephrine is called noradrenaline, hence adrenergic), and are of two sorts- alpha and beta. The alpha-receptors are mainly situated on the muscle cells in the walls of the arterioles, and when stimulated cause the muscle to contract, and hence the arteriole to constrict. Beta receptors are located in several different sites, the most important ones being in the heart, where they stimulate both the strength and speed of contraction, and in the kidney, where they stimulate the release of renin, which is also important in the regulation of blood pressure, as described below.
The adrenergic receptors are the targets for two classes of blood pressure lowering medications, the alpha and beta blocking agents. Both types work on the same general principle: they have some structural similarity to norepinephrine, which enables them to bind to the adrenergic receptors, but unlike norepinephrine, they do not stimulate the receptor to trigger muscle contraction, and they also prevent the norepinephrine from stimulating the receptors. Hence the term blocking agents. The net effect of both alpha and beta blockers is to lower blood pressure, alpha blockers by dilating the arterioles, and beta blockers by lowering cardiac output and shutting off renin release.
The muscle cells in the arterioles are structurally and functionally different from the heart muscle and the muscles in the rest of our body, and are referred to as smooth muscle cells. Their contraction depends on the amount of calcium inside the cell, and in fact the contractile process is triggered by a small amount of calcium passing into the cell through minute pores called calcium channels. The entrance to these channels can be blocked by another group of agents, the calcium channel blockers, which effectively paralyze the smooth muscle cells. Another major mechanism for controlling blood pressure is the renin-angiotensin system. Renin is a chemical which is secreted by the kidney, and circulates in the blood. It has no effects on blood pressure itself, but it leads to the formation of another inert chemical -- Angiotensin One. As it circulates through the lung angiotensin one is converted into angiotensin two by angiotensin converting enzyme. Angiotensin two exerts a very powerful constrictor effect on the arterioles, and thus can raise the blood pressure. It has a second effect, however, which makes it even more potent. It acts on the adrenal gland to release a hormone called aldosterone, which in turn acts on the kidney and causes it to retain sodium. This also tends to raise the blood pressure. One of the normal functions of the renin-angiotensin system is as a defense mechanism to maintain the blood pressure in situations such as hemorrhage or extreme salt depletion. A low blood pressure and a low amount of salt passing through the kidney are two of the three factors which stimulate the kidney to release renin, the third being the sympathetic nervous system.