There are many possible mechanisms which could account for the varied contractile responses of vascular smooth muscle to pharmacologic agents (drugs, KCl and Ca ions). This pharmacologic heterogeneity could be due to extrinsic factors, external to the regulatory characteristics of the smooth muscle cell, such as vessel innervation, orientation of smooth muscle cells, and the connective tissue content. Intrinsic factors which are regulatory in nature could also play a critical role. Chief among these are the mechanism(s) by which vascular smooth muscles regulates the levels of intracellular Ca ions. It is clear that Ca ions interaction with contractile proteins (Ca ions receptor) initiates contraction in vascular smooth muscle as it does in striated muscle. However, despite this acknowledged role of Ca ions, the control of available Ca ions (activator Ca ions) which interacts with the contractile proteins has not been clarified. The basic thrust of this proposal is to assess the various membrane ATPase activities present in vascular smooth muscle which may be involved in ion regulation. To accomplish this, we will study the contents of at least 2 different membrane fractions, a heterogeneous microsomal fraction and a detergent prepared membrane fraction. Enzyme activities to be examined are: Ca ions-ATPase, Mg ions-ATPase, Ca ions plus K ion-ATPase, Na ion-ATPase, K ion-ATPase and Na ion, K ion-ATPase (ouabain inhibited). Their presence has already been identified in the microsomal fractions, but no specific roles have as yet been identified. In the detergent prepared membrane fraction, ouabain inhibited Na, K ion-ATPase is predominant, and a detailed study of this enzyme's characteristics is essential to understanding the potential sarcolemmal role in Ca ions regulation. The assessment of these various enzyme activities will be correlated to various "functional" aspects of the preparations such as a energy-dependent Ca ions sequestration and possible Na ion, Ca ions-exchange. It is hoped that such an approach will identify the relationship between the various ATPases and regulation of contractility in vascular smooth muscle, and help to elucidate the mechanisms controlling pharmagologic heterogeneity.