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Rabbit aortic strips were used to investigate the effect of mitochondrial inhibitors on basal (unstimulated) endothelium dependent relaxation. Since haemoglobin inhibits and the cyclic GMP phosphodiesterase inhibitor, MB22948, amplifies endothelium dependent relaxation they were used to provide evidence of basal activity of endothelium derived relaxing factor (EDRF). Basal activity was not inhibited by incubation with any of three differently acting inhibitors of mitochondrial ATP generation. The mechanism underlying basal EDRF production may thus differ from that of stimulated EDRF production, which is abolished by these mitochondrial inhibitors. [ABSTRACT FROM PUBLISHER]

Endothelium dependent relaxation of isometrically mounted rabbit aortic strip preparations was rapidly inhibited by human plasma at dilutions down to 1:1000. Gel filtration and ion exchange chromatography were used to demonstrate that this inhibitory activity was present in fractions containing haptoglobin. Purified haptoglobin itself possessed no inhibitory action against endothelium dependent relaxation, but the haptoglobin-haemoglobin complex did, consistent with the documented ability of haemoglobin to inhibit this phenomenon. The concentration of haemoglobin normally bound to haptoglobin is sufficient to account for the inhibitory properties of human plasma. This suggests that endothelium derived relaxing factor exerts no downstream intravascular effect in vivo and thus that its physiological dilator role is that of a local autocoid acting on subjacent smooth muscle. [ABSTRACT FROM PUBLISHER]

Objective: In order to elucidate the physiological consequences of irregular vasomotion on microvascular flow we have compared the theoretical hydrodynamic consequences of sinusoidal and chaotic fluctuations in the diameter of a single resistance vessel., Methods: In initial experimental studies vasomotion was induced by histamine in isolated rabbit ear resistance arteries (approximately 150 microns diameter) perfused with physiological buffer under both controlled-flow and controlled-pressure conditions. The phase relationships between the observed oscillations in flow and pressure were used to validate a theoretical electrical circuit in which vasomotion was simulated as sinusoidal or as chaotic fluctuations in distal resistance, with compliance incorporated as a parallel capacitance., Results: In both the experimental and theoretical situation, oscillations in flow led those in pressure by approximately 90 degrees in controlled-flow mode, whereas they were approximately 180 degrees out of phase in controlled-pressure mode. In the theoretical model an increase in the amplitude of sinusoidal or chaotic diameter fluctuations enhanced flow, but "paradoxically" increased both time-averaged resistance and conductance. The model showed that with sinusoidal fluctuations the "efficiency" of perfusion (i.e., flow/viscous work expended in perfusing the vessel undergoing vasomotion) exhibited a peak whose magnitude was a function of vasomotion amplitude and the proximal capacitance in the circuit, and was attributable to transient release of charge from this capacitance. This phenomenon was not observed in simulations with chaotic vasomotion. Hydrodynamic effects specific to the presence of chaotic dynamics (e.g., abrupt increases or decreases in flow under the variation of a single parameter) were also evident when the intrinsic complexity of the vasomotion, rather than its amplitude, was varied., Conclusions: The model suggests (i) that vasomotion may serve to increase flow, (ii) that conductance provides a more accurate physiological measure of the functional consequences of active vasomotion than resistance, (iii) that chaotic vasomotion dissipates transients more readily than sinusoidal vasomotion, thereby conferring greater stability to microcirculatory perfusion and (iv) that specific modes of chaotic vasomotion may influence flow independently of their amplitude.