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

Burton, Gerardine A., Griffith, T. M. and Edwards, David Hughes 1989. EDRF-mediated dilatation in the rat isolated perfused kidney: a microangiographic study. British Journal of Pharmacology 98 (4) , pp. 1207-1212. 10.1111/j.1476-5381.1989.tb12666.x

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1 X-ray microangiographic techniques were used to study the influence of endothelium-derived relaxing factor (EDRF) on vasomotion in the isolated, intact, buffer-perfused kidney of the rat. The main renal (R0), segmental (R1) and interlobar (R2) arteries (control diameters ca. 600, 400 and 300 μm respectively) were studied quantitatively. 2 Inhibition of basal EDRF activity by haemoglobin (1 μm) did not elevate perfusion pressure or constrict R0, R1 and R2 in control preparations, implying a low level of spontaneous myogenic tone. In preparations preconstricted by 0.3 μm methoxamine, haemoglobin caused a further rise in perfusion pressure and amplified constrictor responses in R1 and R2 while also inducing ‘paradoxical’ dilatation of R0. 3 A spatially heterogeneous pattern of diameter responses (constriction of R2 and R1 with minimal dilatation of R0) was observed with two concentrations of methoxamine (0.3 μm and 3 μm). The magnitude of these responses was, however, smaller with 3 μm than 0.3 μm methoxamine, even though it increased perfusion pressure to a greater extent (88 mmHg cf. 24 mmHg). This ‘paradoxical’ behaviour indicates more pronounced constriction of distal arteries (which could not be resolved quantitatively) with 3 μm methoxamine. 4 In contrast to the heterogeneity of constrictor responses induced by methoxamine, the dilator action of acetylcholine was spatially homogeneous: log IC50 values calculated from the diameter changes induced in R0, R1 and R2 were similar and, moreover, equivalent to that calculated from the corresponding alterations in perfusion pressure. The fall in perfusion pressure induced by an approximately median effective concentration of acetylcholine (0.3 μm) was completely reversed by haemoglobin, consistent with the involvement of EDRF, although, reversal of the acetylcholine-induced dilatation of R0, R1 and R2 was not observed. 5 The results are consistent with the idea that constriction of distal vessels can attenuate and even directionally reverse intrinsic constrictor responses in the proximal R0, R1 and R2 ‘feed’ arteries by producing an overriding increase in ‘upstream’ pressure. This effect explains the paradoxical dilatation of R0 induced by haemoglobin in the presence of 0.3 μm methoxamine, the smaller magnitude of the diameter changes induced in R0, R1 and R2 by 3 μm as compared to 0.3 μm methoxamine, and the failure of haemoglobin to reverse the acetylcholine-induced dilatation of R0, R1 and R2.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 0007-1188
Last Modified: 04 Jun 2017 07:59

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