Arterial internal elastic lamina holes: relationship to function?

Abstract

Internal elastic lamina (IEL) hole (fenestration) characteristics and myoendothelial gap junction (MEGJ) density were examined in selected resistance and conduit arteries of normal and diseased rat and mouse models, using conventional, ultrastructural and confocal microscopy methods. Selected vessels were those commonly used in functional studies: thoracic aorta, proximal and distal mesenteric, caudal, saphenous, middle-cerebral and caudal cerebellar artery. Rat and mouse strains and treatment groups examined were Dahl, Sprague Dawley, Wistar Kyoto, Wistar, spontaneously hypertensive (SHR), deoxycorticosterone (DOC) treated rat; and apolipoprotein E knockout, C57/BL6 and BALB/c mice. Vessel size (as IEL circumference), IEL hole and MEGJ density were quantified. In mesenteric arteries, the width of IEL holes and the percent of IEL occupied by holes were also determined. IEL hole density varied significantly within and between mesenteric artery beds, even among normotensive rat strains. Among the hypertensive rats (SHR and DOC), hole density in some vessels was higher in the normotensives than in the hypertensives within each strain, whereas in Dahl rats, hole density was similar between hypertensives and normotensives. Hole density was not correlated with the formation of intimal lesions in superior mesenteric artery. There was no positive general correlation between IEL hole and MEGJ density in resistance and conduit vessels. However, there was a positive correlation between the size of some resistance arteries and MEGJ density, although such a relationship did not hold for conduit vessels or during development, and there was no such relationship between vessel size and IEL hole density. Whilst IEL holes are obviously required for MEGJ communication, their presence is not an indication of contact-mediated communication, but rather may be related to the presence of sites for the low resistance passage of diffusion-mediated release of vasoactive endothelial and smooth muscle substances.

Fig. 1

Intimal lesion, internal elastic lamina (IEL) hole, myoendothelial gap junction lesion characteristics in selected male rat and mouse vessels. Intimal lesions (*) in rat superior mesenteric (SMA), with endothelial (ec), elastic laminae (el) and smooth muscle cells (smc), and SHR caudal artery (A,B, respectively). Autofluorescence of IEL with IEL holes as intermittent dark spots (arrows); adult male rat mesenteric (primary, Ci; and tertiary, Cii branch); lateral saphenous (D), and distal caudal (E) artery, as potential sites for passage of ec and smc projections associated with heterocellular gap junction or low resistance communication pathways between ecs and smcs. Scanning electron microscopy shows such holes as pits in the luminal IEL surface (F, arrows, rat aorta). Transmission electron microscopy of IEL holes shows the gap in the IEL typical for such holes (*) in resistance and conduit vessels (G,H, rat mesenteric and juvenile (2 wk) male mouse aorta, respectively). Myoendothelial gap junction from juvenile mouse thoracic aorta (I) with typical pentalaminar gap junction membrane density (inset, arrowed). Bars: A, 10 µm; B, 5 µm; C–F, 20 µm; G, 1 µm; H,I, 2 µm.