MECHANISMS OF PLATELET-INDUCED ANGIOSPASTIC REACTIONS - POTENTIATION OF CALCIUM SENSITIVITY

Platelet aggregation and adherence to the vessel lumina are common eve nts in various physiological and pathological conditions. However, the mechanisms whereby aggregating platelets cause vasoconstriction remai n unclear. We hypothesized that aggregating platelets may alter the Ca 2+ sensitivity of the contractile apparatus in smooth muscle cells. We tested this hypothesis using rabbit common carotid arteries permeabil ized with beta-escin. In these preparations, the receptor-effector cou pling is functionally intact, while the intracellular ionic compositio n, in particular calcium concentration, may be clamped. Aggregating pl atelets in the presence of 100 mu M GTP left-shifted the pCa-force cur ve. On average, the pD(2) 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-p roteins with guanosine 5'-O-(2-thiodiphosphate). Platelets modulated c alcium sensitivity at concentrations markedly lower than those that pr oduce contractions of intact vessels. These data suggest that platelet activation in the vicinity of the vessel wall may sensitize the smoot h muscle contractile apparatus to calcium via a G-protein-dependent me chanism. This phenomenon may enhance vessel responses to vasoactive su bstance that produce vessel contraction via elevation of intracellular calcium concentrations.