Remodelling and Enhanced Myogenic Tone in Cerebral Resistance Arteries Isolated from Genetically Hypertensive Brattleboro Rats

Abstract

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.