Proceedings of the Symposium on Cardiovascular Science and Medicine: From Bench to Bedside ENDOTHELIUM-SMOOTH MUSCLE INTERACTIONS IN BLOOD VESSELS

SUMMARY 1. Blood vessel tone is determined both by smooth muscle and endothelial functions. In coronary arteries taken from rat (Fisher-Lewis) cardiac transplanted hearts, the inducible form of NOS (LNOS) in smooth muscle is more active, while acetylcholine-induced nitric oxide production in the endothelium is greatly diminished. This causes a greatly reduced myogenic constriction, in pressurized septal arteries taken from immunologically challenged transplanted hearts. 2. The sarcoplasmic reticulum (SR) of smooth muscle and the endoplasmic reticulum (ER) of endothelial cells sequester Ca2+ from the cytoplasm. This reduces the intracellular concentration of free Ca", which is necessary for the activation of cellular processes. The release of Ca2+ from internal stores occurs through ryanodine and IP3 recoptors located on the SR membrane. 3. The superficial SRlER also interacts with ion exchangers and pumps in the plasma membrane. This allows for the superficial SRER to function in Ca2+ extrusion; for example, inhibition of the SRER Ca2+-ATPase (SERCA) partially inhibits the rate of loss CaZ+ from the cell. Recent data suggest that the SR Ca2+-ATPase and the Na+-Cazc exchanger of smooth muscle cells function in series; that is, Ca" uptake by the SR followed by release towards the exchanger to mediate extrusion. This interaction between the SERCA of the superficial SR and ion exchangers and pumps creates intracellular Ca2+ gradients. 4. The SERCA of the superficial, peripherally distributed SR/ER also serves to regulate Ca2+ entry from the extracellular space. This occurs in part by inhibition of the superficial buffer barrier function of the SR as well as by depletion of stimulated Ca2+ entry. 5. Cat+ entry is also regulated in endothelial and smooth muscle cells by the membrane potential. Membrane hyperpolarization increases the driving force for Ca" entry into endothelial cells, which lack voltage-gated Ca2+ channels, and reduces open