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EDRF‐mediated dilatation in the rat isolated perfused kidney: a microangiographic study
Author(s) -
Burton Gerardine A.,
Griffith T.M.,
Edwards D.H.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12666.x
Subject(s) - methoxamine , perfusion , dilator , vasoconstriction , constriction , vasodilation , medicine , endothelium derived relaxing factor , electrical impedance myography , chemistry , anatomy , cardiology , receptor , agonist
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 (R 0 ), segmental (R 1 ) and interlobar (R 2 ) arteries (control diameters ca. 600, 400 and 300 μ m respectively) were studied quantitatively. 2 Inhibition of basal EDRF activity by haemoglobin (1 μ m ) did not elevate perfusion pressure or constrict R 0 , R 1 and R 2 in control preparations, implying a low level of spontaneous myogenic tone. In preparations preconstricted by 0.3 μ m methoxamine, haemoglobin caused a further rise in perfusion pressure and amplified constrictor responses in R 1 and R 2 while also inducing ‘paradoxical’ dilatation of R 0 . 3 A spatially heterogeneous pattern of diameter responses (constriction of R 2 and R 1 with minimal dilatation of R 0 ) was observed with two concentrations of methoxamine (0.3 μ m and 3 μ m ). The magnitude of these responses was, however, smaller with 3 μ m than 0.3 μ m 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 μ m methoxamine. 4 In contrast to the heterogeneity of constrictor responses induced by methoxamine, the dilator action of acetylcholine was spatially homogeneous: log IC 50 values calculated from the diameter changes induced in R 0 , R 1 and R 2 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 μ m ) was completely reversed by haemoglobin, consistent with the involvement of EDRF, although, reversal of the acetylcholine‐induced dilatation of R 0 , R 1 and R 2 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 R 0 , R 1 and R 2 ‘feed’ arteries by producing an overriding increase in ‘upstream’ pressure. This effect explains the paradoxical dilatation of R 0 induced by haemoglobin in the presence of 0.3 μ m methoxamine, the smaller magnitude of the diameter changes induced in R 0 , R 1 and R 2 by 3 μ m as compared to 0.3 μ m methoxamine, and the failure of haemoglobin to reverse the acetylcholine‐induced dilatation of R 0 , R 1 and R 2 .