Mechanisms of platelet-induced angiospastic reactions: potentiation of calcium sensitivity

Abstract

Platelet aggregation and adherence to the vessel lumina are common events in various physiological and pathological conditions. However, the mechanisms whereby aggregating platelets cause vasoconstriction remain unclear. We hypothesized that aggregating platelets may alter the Ca2+ sensitivity of the contractile apparatus in smooth muscle cells. We tested this hypothesis using rabbit common carotid arteries permeabilized with beta-escin. In these preparations, the receptor-effector coupling is functionally intact, while the intracellular ionic composition, in particular calcium concentration, may be clamped. Aggregating platelets in the presence of 100 microM GTP left-shifted the pCa-force curve. On average, the pD2 for calcium was 6.30 +/- 0.05 and 6.86 +/- 0.07 in the absence and presence of platelets, respectively (p < 0.01). This increase in calcium sensitivity was prevented by blockade of G-proteins with guanosine 5'-O-(2-thiodiphosphate). Platelets modulated calcium sensitivity at concentrations markedly lower than those that produce contractions of intact vessels. These data suggest that platelet activation in the vicinity of the vessel wall may sensitize the smooth muscle contractile apparatus to calcium via a G-protein-dependent mechanism. This phenomenon may enhance vessel responses to vasoactive substance that produce vessel contraction via elevation of intracellular calcium concentrations.