ENDOTHELIUM-SMOOTH MUSCLE INTERACTIONS IN BLOOD-VESSELS

1. Blood vessel tone is determined both by smooth muscle and endotheli al functions. In coronary arteries taken from rat (Fisher-Lewis) cardi ac transplanted hearts, the inducible form of NOS (iNOS) in smooth mus cle is more active, while acetylcholine-induced nitric oxide productio n in the endothelium is greatly diminished. This causes a greatly redu ced myogenic constriction, in pressurized septal arteries taken from i mmunologically challenged transplanted hearts. 2. The sarcoplasmic ret iculum (SR) of smooth muscle and the endoplasmic reticulum (ER) of end othelial cells sequester Ca2+ from the cytoplasm. This reduces the int racellular concentration of free Ca2+, which is necessary for the acti vation of cellular processes. The release of Ca2+ from internal stores occurs through ryanodine and IP3 recoptors located on the SR membrane . 3. The superficial SR/ER also interacts with ion exchangers and pump s in the plasma membrane. This allows for the superficial SR/ER to fun ction in Ca2+ extrusion; for example, inhibition of the SR/ER Ca2+-ATP ase (SERCA) partially inhibits the rate of loss Ca2+ from the cell. Re cent data suggest that the SR Ca2+-ATPase and the Na+-Ca2+ exchanger o f smooth muscle cells function in series; that is, Ca2+ uptake by the SR followed by release towards the exchanger to mediate extrusion. Thi s interaction between the SERCA of the superficial SR and ion exchange rs and pumps creates intracellular Ca2+ gradients. 4. The SERCA of the superficial, peripherally distributed SR/ER also serves to regulate C a2+ entry from the extracellular space. This occurs in part by inhibit ion of the superficial buffer barrier function of the SR as well as by depletion off stimulated Ca2+ entry. 5. Ca2+ entry is also regulated in endothelial and smooth muscle cells by the membrane potential. Memb rane hyperpolarization increases the driving force for Ca2+ entry into endothelial cells, which lack voltage-gated Ca2+ channels, and reduce s open state probability of voltage-gated Ca2+ channels in vascular sm ooth muscle cells. The two cell types have electrical contact and inte ract in a dynamic manner to regulate blood vessel diameter.