How Drugs Work

Background

Cardiovascular Physiology

In order to break down the different pharmacological treatments of hypertension (as well as primary prevention techniques), it is imperative to have a basic understanding of the pathophysiology of the cardiovascular system. As eluded in the name, the cardiovascular system has two main components, the heart (cardio), and vasculature (arteries, capillaries, veins, etc.). There are micro and macro ways of analyzing the cardiovascular system. To start, a micro view of the system focuses on the basic needs of the cells dispersed throughout the body. All cells of the body require the input of at least two things, oxygen and glucose, and the output of at least one thing, carbon dioxide. This is accomplished by a process known as perfusion. Without good perfusion in a tissue in the body, the cells within that tissue will soon die. Loss of perfusion can lead to a cascade of local cell death. When thinking of the cardiovascular system, its pathophysiology, and related pharmacology, it is easy to forget the fundamental biology that the cardiovascular system was created for. While humans are living breathing complex organisms, it is important not to forget that we are ultimately a formation of millions of cells that require transfer of oxygen, glucose, and carbon dioxide. Needless to say, the cardiovascular system has a big responsibility for maintaining the homeostasis, or balanced living, of all the body's cells.

This unit will briefly discuss the heart and its vessels; however, if more information on the entire cardiovascular system is desired, it is suggested to reference the units Under Pressure! The Circulatory System and Hypertension by Vanessa Vitug or Building a Heart: The Function and Mechanics by Eric Laurenson.

The heart is a pump that utilizes muscles to create pressure differences to move blood. Blood, as with any liquid, travels from areas of high pressure to low pressure. The pressure gradients created by the heart are determined by three factors: the amount of contractile force made by the heart (or how hard the heart muscle contracts when pumping blood), the amount of fluid the heart has to pump, and the amount of resistance in the vascular system. Once pressure is created in the heart (through contractions of heart tissue) blood is expelled into vessels called arteries. Arteries contain three layers: tunica intima, tunica media, and tunica adventitia. The intima, or inner layer (think of it as being intimate with the blood), contains only a single layer of endothelial cells. The media, or middle layer, is the thickest layer, and contains smooth muscle that allow for control of vessel radius. The adventitia, or outer layer, contains accessory tissue, and will not be discussed in this unit. ² Throughout the duration of this unit when the word vessel is used it is referencing the arterial system. The venous system is not emphasized in this unit, as hypertension affects primarily the arterial tissues, and it is these vessels that are the targets for pharmacological agents to alter blood pressure.

For the remainder of this unit, the cardiovascular system will be discussed on a macro scale. When discussing the effectiveness of the cardiovascular system, it is important to be able to quantify its efficacy. Cardiac output, which is one way of measuring the efficacy of the heart, is measured by both the heart's ability to pump blood (cardio), and the vessels ability to distribute the blood (vasculature). The formula used to calculate the efficiency of the heart can be found in Figure One. Cardiac output (CO) (measured in milliliters per minute) equals the rate of heart contractions (also known as heart rate (HR), measured in beats per minute), multiplied by the amount of fluid that the heart expels on each beat (also known as the stroke volume (SV), measured in milliliters per beat). For example, a normal HR (70 bpm) multiplied by a normal SV (70 mL/min) gives a cardiac output of 4900 mL/min. In other words, the heart is able to pump approximately the equivalence of two and a half 2L sodas within a one minute time period! As one exercises, the body's cells require even more circulating blood. In many instances, exercise can increase CO sevenfold! That is comparable to 35L (or 17.5 2L soda bottles) pulsing through your body in one minute. On the other hand, if CO drops below what is necessary to maintain cellular homeostasis, problems can ensue, because at the micro level cells in the body will not receive the substrates that they need for their function. ³

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