Fractal analysis of role of smooth muscle Ca2+ fluxes in genesis of chaotic arterial pressure oscillations.

We have investigated the role of vascular smooth muscle Ca2+ fluxes in the genesis of chaotic pressure oscillations induced by histamine in isolated resistance arteries from the rabbit ear. The responses exhibited distinct "fast" and "slow" components, with periods of 5-20 s and 1-5 min, respectively, which could be dissociated pharmacologically. The fast subsystem involved ion movements at the cell membrane and was inhibited by both low (< 2 mM) and high (> 5 mM) extracellular Ca2+ concentration ([Ca2+]o) by verapamil (which inhibits voltage-dependent Ca2+ influx) and by charybdotoxin (ChTX) and apamin (which block Ca(2+)-activated K+ channels). In contrast, the slow subsystem was intracellular and was selectively attenuated by ryanodine, which inhibits Ca(2+)-induced Ca2+ release from sarcoplasmic reticulum. The effects of these interventions on the complexity of the responses were quantified by calculating their fractal dimension, a parameter that estimates the minimum number of independent variables contributing to an irregular time series. Its mean value was generally > 2 under control conditions but decreased to < 2 in a concentration-dependent fashion in the presence of verapamil, ChTX, apamin, or ryanodine and when [Ca2+]o was outside the range of 2-3 mM. Each intervention thus removed one dimension of complexity from the mechanisms generating the rhythmic activity. We conclude that the interaction of a fast membrane oscillator, which involves Ca2+ influx, Ca(2+)-activated K+ efflux, and therefore presumably changes in membrane potential, and a slow intracellular oscillator involving Ca2+ sequestration and release from stores is responsible for vascular chaos in our model. The coupling between these subsystems is likely to be mediated by cytosolic [Ca2+].