Pharmacological implications of the flow-dependence of vascular smooth muscle tone

The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to changes in blood flow. These changes in blood flow can secondarily change vascular diameter, thus complicating the basic response. Furthermore, drugs can modify the local flow-sensitive mechanism directly. The flow-initiated effect seems to depend, both qualitatively and quantitatively, on the level of wall tone and is not entirely endothelium-dependent. If the primary action of a drug is to alter the tone level of vascular smooth muscle directly or if tone changes as a result of a change in blood pressure (and thus in local myogenic control), then it follows that these changes in turn influence the flow response, both quantitatively and qualitatively. The vascular response to flow is complex both in its site of origin and the functional changes initiated. It is not synonymous with the endothelial-dependent action of acetylcholine.