Ca2+ Oscillations Regulate Contraction Of Intrapulmonary Smooth Muscle Cells

Pulmonary blood pressure is a function of the resistance of the intrapulmonary blood vessels. Consequently, the mechanisms controlling blood vessel smooth muscle cell (SMC) contraction serve as potential sites for hypertension therapy. To explore these mechanisms, access to the intrapulmonary vessels is required and this is provided by the observation of a unique lung slice preparation with microscopy. There are 2 major processes that determine SMC tone; the intracellular Ca2+ concentration and the sensitivity of the SMCs to Calf. Agonist-induced increases in Ca2+ occur in the form of propagating Ca2+ oscillations that predominately utilize internal Ca2+ stores and inositol trisphosphate receptors. The frequency of these Ca2+ oscillations correlates with contraction. Agonists also increase Ca2+ sensitivity of SMCs to enhance contraction. Changes in membrane potential mediated by KCl also stimulate contraction via slow Ca2+ oscillations and increased sensitivity. However, these slow Ca2+ oscillations rely on Ca2+ influx to drive the cyclic release of over-filled Ca2+ stores via the ryanodine receptor. The relaxation of SMC tone can be induced by the reduction of the frequency of the Ca2+ oscillations and the Ca2+ sensitivity by b(2)-adrenergic agonists or nitric oxide.