Ca²⁺ Oscillations Regulate Contraction Of Intrapulmonary Smooth Muscle Cells

Abstract

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 Ca²⁺. 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 b₂-adrenergic agonists or nitric oxide.