This chapter has a different emphasis from others in this book because it is written from the perspective of integrative physiology. Our objective is to discuss the conditions that endothelial cells (ECs) are exposed to in the body from the luminal side and to raise a number of questions that may influence how vascular biologists think about their subject. In this context, new data may be required to determine whether these are just theoretical considerations or whether they are, in fact, actual perturbations for these cells. If the latter were true, one must consider how these perturbations are dealt with and whether they have an impact on EC function.

Our first task will be to define the composition of blood in the arterial tree. The description will be expanded to veins draining specific regions of individual organs where large differences in blood composition occur. Perhaps the best example of this latter point is the marked difference in the composition of venous blood draining the renal cortex as compared with that draining the hypoxic, hypertonic, and hypercarbic renal medulla.

Rather than focusing on many compounds, we emphasize the major volatile gases (oxygen [O2], carbon dioxide [CO2], and ammonia[NH3]); ions such as hydrogen (H+), potassium (K+), calcium (Ca2+) and citrate; as well as water because of their biological importance and implications for normal cell function. Where applicable, the discussion in each section is divided into three parts. First, we describe the composition of blood in each vascular location. Second, we ask: “What demands might be placed on ECs because of their exposure to the composition of blood in their lumen?”