In this study, we examined the structural and functional properties of cerebral resistance arteries isolated from normotensive (Di/N), and hypertensive (Di/H), vasopressin-deficient rats. Di/H rats had a significantly higher mean arterial blood pressure (MAP, 159 ± 3 mm Hg) than Di/N rats (125 ± 2 mm Hg). Vessels were set up in a pressure myograph, and the internal diameter and wall thickness were determined at increasing intraluminal pressures under passive (calcium-free) conditions. Arteries were then pressurized to the MAP of the animal, from which they were isolated and fixed with glutaraldehyde, embedded in araldite, sectioned and examined histologically. Under passive conditions, the middle cerebral artery (MCA) from Di/H rats had a smaller internal diameter than the MCA isolated from Di/N rats at all distending pressures. This smaller internal diameter of vessels from hypertensive rats is characteristic of eutrophic inward remodelling, whereby a similar amount of wall material is organized around a smaller lumen, without vascular growth or an alteration in artery distensibility. We have previously shown that similar structural alterations occur in mesenteric resistance arteries isolated from Di/H rats. In the presence of extracellular calcium (1.6 mmol/l), the MCA isolated from Di/H rats had significantly more intrinsic tone than the MCA isolated from Di/N rats in the pressure range of 10–110 mm Hg, although arteries from both strains had a similar myogenic index. The increased intrinsic constriction was a specific enhancement of pressure-induced tone, since responses to the thromboxane mimetic, U46619, were decreased, rather than increased, in the MCA isolated from Di/H rats. Furthermore, it is unlikely that the increased intrinsic tone in arteries isolated from Di/H rats was due to an impaired endothelial function since responses to the endothelium-dependent vasodilator, bradykinin, were enhanced in these vessels compared to arteries isolated from Di/N rats.

Human isolated cerebral resistance arteries spontaneously contract when exposed to raised intravascular pressure. This pressure-induced myogenic response may contribute to cerebral autoregulation of blood flow.

1 This study examined the ability of basal nitric oxide activity to suppress intrinsic and vasoconstrictor tone in isolated rings of porcine cerebral artery. 2 Following stretch of approximately 1 g, N G -nitro-L-arginine methyl ester (L-NAME, 100 mM) produced a rise in tone in endothelium-containing but not endothelium-denuded rings. Thus, intrinsic tone was present and was powerfully suppressed by basal nitric oxide activity. 3 Nevertheless, when concentration-response curves were constructed to U46619 and 5-hydroxytryptamine (5-HT), no endothelium-dependent depression of vasoconstriction was observed. It therefore appeared that basal nitric oxide activity was able to suppress intrinsic but not vasoconstrictor tone in these vessels. 4 Stretch-tension curves generated following the application of stretch over the range 0 ± 5.5 g on endothelium-denuded rings showed that tension was stretch-induced. Experiments conducted in the presence of L-NAME (100 mM) revealed that the level of tone present in endothelium-containing rings was substantially higher than in endothelium-denuded rings across the entire range of stretch. 5 When endothelium-containing and endothelium-denuded rings were set at similar levels of stretch-induced tone, rather than similar levels of stretch, the presence of the endothelium now depressed signi®cantly vasoconstrictor responses to U46619 and 5-HT. 6 Thus, when endothelium-containing and endothelium-denuded rings of porcine cerebral artery are set at similar points along their respective stretch-tension curves, rather than at similar levels of stretch, basal nitric oxide activity can be seen to inhibit both stretch-induced and vasoconstrictor tone.