EDRF coordinates the behaviour of vascular resistance vessels

Abstract

Constriction of vascular smooth muscle in response to the stimulus of raised intravascular pressure--the myogenic response--represents a positive feedback mechanism which, if unopposed, could theoretically lead to instability in the intact circulation. Dilation in response to increased intraluminal flow would provide an opposing feedback mechanism which could confer overall stability. Flow-dependent dilation in conduit vessels is mediated by endothelium-derived relaxing factor (EDRF), but the relationship between flow and EDRF activity has not been studied in resistance vessels in situ. We here demonstrate that EDRF can coordinate the aggregate hydrodynamic properties of an intact network. Under control conditions, EDRF maintains a fourth-power relationship between diameter and flow so that the pressure gradient in each vessel asymptotically approaches a constant value at high flow rates. Basal EDRF release may also maintain a similar spatial distribution of flow at different flow rates, even under conditions of moderate pharmacological constriction.

EDRF‐mediated dilatation in the rat isolated perfused kidney: a microangiographic study

“…Haemoglobin appears to be a specific inhibitor of EDRF activity at the concentration employed (1 gM) (Martin et al, 1985;Edwards et al, 1986;Kelm et al, 1988;Nishiye et al, 1989 (Cocks & Angus, 1983;Miller & Vanhoutte, 1985;Egleme et al, 1984;Matsuda et al, 1985), there is no evidence that al-adrenoceptors can do so in any species or artery type. The lack of effect of haemoglobin in the absence of a constrictor agonist in this preparation differs from previous experiments with the rabbit isolated ear, in which inhibition of basal EDRF activity induced a small but significant rise in perfusion pressure in the absence of exogeneous constrictor agents and in which haemoglobin therefore unmasked myogenic tone (Griffith et al, 1987). (Winquist, 1988 'feed' vessels thus allows inferences to be made about the behaviour of the distal vasculature of these rat isolated kidney preparations.…”

“…The microangiographs were analysed by a semiinteractive image analysis system as previously described (Griffith et al, 1987;. A calibrated gold grid was placed on the surface of each kidney to determine magnification factors (approximately x 3) accurately.…”

“…Basal release of EDRF (i.e. spontaneous release in the absence of any exogeneous pharmacological agent) also exerts a major effect on pressure-flow and diameter-flow relationships in the vascular network of the rabbit ear (Griffith et al, 1987;1989) and the rat mesentery (Randall & Hiley, 1988).…”

“…Microangiographic techniques (Griffith et al, 1987;1989) were used to measure diameter changes in the three primary sets of arteries of the rat kidney (down to approximately 200ym in size). In combination with simultaneous measurement of pressure changes, this information allows inferences to be made about the responses of more distal vessels which cannot be visualized directly in this preparation by microangiography.…”

Intravascular pressure-evoked changes in intracellular calcium [Ca2+]i and tone in rat mesenteric and rabbit cerebral arteries in vitro

“…This phenomenon was first noted by Bayliss in 1902 1 and although originally observed in larger arteries, it is most strongly expressed in small arteries and arterioles, 2,3 where it is functionally important in the process of circulatory blood flow autoregulation and acts in conjunction with flowmediated vasodilation to regulate arterial diameter. 4 In the same way that agonist mediated contractile responses in vascular smooth muscle are dependent on mobilisation of intracellular calcium ([Ca 2+ ] i ), the myogenic response is also believed to depend on a rise in [Ca 2+ ] i . 3,5 Myogenic contractile responses appear to be especially dependent on influx of extracellular Ca 2+ and can be abolished by the removal of extracellular calcium or the application of calcium channel blockers.…”