Endothelium-derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear.

1. Microradiographic techniques have been used to show that endothelium-derived relaxing factor (EDRF), which is believed to be nitric oxide, influences vasomotor responses in small arteries and arterioles down to 25 micron in diameter in an isolated, intact, buffer-perfused ear preparation of the rabbit. Arteries down to 75 micron in diameter, i.e. the central ear artery (G0) and its first three generations of branch vessels (G1, G2 and G3) were studied quantitatively. 2. Relative constrictor responses to 1 micron 5-hydroxytryptamine (5-HT) and the combination of 1 microM 5-HT and 1 microM histamine diminished progressively from G0 to G3. Constrictor responses to 5-HT were doubled in all generations by 1 microM haemoglobin which abolishes EDRF activity. 3. Relative dilator responses to acetylcholine or to substance P in preconstricted arteries were, in contrast, equal in the different generations. Mean -log (IC50) values calculated from diameter measurements were 7.63 +/- 0.10 M and 9.80 +/- 0.11 M, respectively. These dilator responses were abolished by 1 microM haemoglobin, implying that they were EDRF-mediated. Spatial homogeneity of relative dilator responses was found also with glyceryl trinitrate (10 or 50 microM) whose activity is thought to depend on biotransformation to nitric oxide, in both the presence and the absence of haemoglobin. 4. This finding of spatial homogeneity of the diameter response to changes in EDRF activity (or to glyceryl trinitrate) implies that EDRF influences hydrodynamic resistance more in vessels where constrictor tone is high.