Excitation of vascular muscle by norepinephrine

The mechanism by which norepinephrine causes excitation of vascular muscle is a concept that has undergone considerable change in the last several years. Although the excitation step is absolutely fundamental to understanding constriction and dilation of arteries, several aspects of the hypothesis are not well understood and have recently been controversial. The earliest view of the excitation process was that action potentials propagate uniformly along the arterial wall, just as in fast skeletal muscle, and was disproved early in recording of electrical events from blood vessel walls. The view that then emerged was that membrane potential acts as an analog signal controlling contraction through graded depolarization which, unlike that found in fast skeletal or cardiac muscle, could be maintained for minutes or even hours. This concept of graded depolarization and graded contraction has served as the best model of the vascular muscle excitation process for about 20 years. However, questions have been raised about the importance of membrane potential as a control mechanism because of reports of noncorrelations between membrane potential and tension. The controversy centers around two alternate proposals for the excitatory action of norepinephrine. The proposal of the noncorrelation group is that mechanisms other than membrane potential exert the major control over contraction, perhaps with spatially specialized receptors such that only those areas near nerve endings would cause depolarization as part of the event initiating contraction. On the other hand, the proposal by the strong correlation group would be that membrane potential is the dominant control mechanism. Where experiments have been carried out to specifically test the existence of a noncorrelation between membrane potential and contraction, no failure of correlation was found. The fundamental problem in each instance of a noncorrelation appears to be the attempt to record tension from one part of an artery and membrane potential from another part, which is assumed to behave as an electrically and mechanically homogeneous unit. However, direct measurements of localized areas of the blood vessel wall show such an assumption to be unjustified. In fact, cell-to-cell conduction of an electrical signal to synchronize the blood vessel could not be supported in experiments using refined intracellular and extracellular recording methods. These observations suggest that the attempt to understand the relationship between interaction of norepinephrine with the membrane and the contractile event is best approached as a single cell phenomenon, where assurance that electrical and mechanical recording is of the same process can be demonstrated. At least in the caudal artery of the rat, the spatial definition of contraction appears to be under the control of diffusion of norepinephrine. No important role for cell-to-cell conduction or for modification of the excitation process by any agent through changes in conduction has been demonstrated in vascular muscle. The extent of the arterial wall involved in a single contraction would appear to be defined by diffusion of norepinephrine from its release point.