Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats.

Abstract

The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril and hydralazine reduced systolic arterial pressure (from 195±8 to 125±5 and 148±3 mm Hg, respectively [mean±SEM]; p<0.05). To examine structure and mechanics of cerebral arterioles, we measured pressure (servonull), external diameter, and cross-sectional area of the vessel wall (histologically) in pial arterioles of normotensive Wistar-Kyoto (WKY) rats and SHRSP that were untreated or that were treated for 3 months with cilazapril or with hydralazine. Arterioles were maximally dilated with EDTA. In WKY rats, cilazapril and hydralazine did not alter pial arteriolar pressure, external diameter, or cross-sectional area of the vessel wall. In SHRSP, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to levels not significantly different from WKY rats (from 1,911±155 to l,244±101 and l r 388±59 /im\ respectively, compared with l,405±95 /tm 2 for untreated WKY rats). Cilazapril was more effective than hydralazine in reducing pial arteriolar pressure (from 110 ±6 to 62 ±2 mm Hg with cilazapril versus 79 ±5 mm Hg for hydralazine compared with 60±4 mm Hg for untreated WKY rats). Cilazapril, but not hydralazine, attenuated reductions in external diameter of pial arterioles (from 91 ±4 to 100 ±4 (tm for cilazapril versus 91 ±3 fim for hydralazine compared with 107 ±3 fim for untreated WKY rats). Stress-strain curves indicate that cilazapril was more effective than hydralazine in attenuating increases in distensibility of pial arterioles in SHRSP. Both treatments prevented the occurrence of stroke in SHRSP, whereas eight of 15 untreated SHRSP developed strokes. Thus, both an ACE inhibitor and hydralazine prevented hypertrophy of cerebral arterioles and stroke in SHRSP, even though the ACE inhibitor was more effective than hydralazine in lowering intra-arteriolar pressure. In contrast, only the ACE inhibitor attenuated increases in distensibility and "remodeling" (reduction in external diameter) of cerebral arterioles, perhaps due to its greater efficacy in reducing pial arteriolar pressure at the doses used in this study. These findings suggest that determinants of distensibility and vascular remodeling may be different from determinants of vascular hypertrophy. (Hypertension 1991;17:308-316) C hronic hypertension alters the composition and mechanics of both large and small cerebral blood vessels. Large cerebral arteries undergo hypertrophy, with an increase in collagen content, and compliance is reduced in spontaneously hypertensive rats (SHR) 12 and stroke-prone SHR (SHRSP). 34 In contrast, compliance of cerebral arterioles is paradoxically increased in SHRSP, despite

Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension.

“…Another factor that has recently been suggested to play a role in both the induction and regression of vascular hypertensive damage is pulse pressure. 31 In the present study there were no differences in pulse pressure between both groups of patients. Other factors that may be involved in vascular hypertrophy and remodeling in hypertension include the sympathetic nervous system 32 and growth factors such as transforming growth factor-/31, basic fibroblast growth factor, and platelet-derived growth factor 23 as well as other agents and cytokines.…”

“…Interestingly, in cerebral arterioles of stroke-prone spontaneously hypertensive rats, an increased distensibility has been demonstrated together with remodeling, and cilazapril treatment corrected both the remodeling and mechanical changes present. 31 This normalization of structure and mechanics of cerebral arterioles was associated with changes in the relative composition of nondistensible (collagen, basement membrane) and distensible (smooth muscle, elastin, endothelium) components. 34 Our study does not allow us to determine whether effects similar to those produced by the same converting enzyme inhibitor in cerebral arterioles of hypertensive rats were also induced in this group of hypertensive humans.…”

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

“…5). The mildly neuroprotective anaesthesic agent, pentobarbitone, was used in 12 reports on SHR-SP (Sadoshima et al, 1983;Tamaki et al, 1984;Werber and Heistad, 1984;Mayhan et al, 1987Mayhan et al, , 1988Baumbach et al, 1988Baumbach et al, , 1994Hajdu et al, 1991;Yang et al, 1991Yang et al, , 1993Chillon and Baumbach, 1999;Maguire et al, 2004) and in 4 other studies (Rosenberg et al, 1990;Toshima et al, 2000;Whitehead et al, 2005a, b). The primate aortic coarctation studies used ketamine anaesthesia (Kemper et al, 1999(Kemper et al, , 2001Moore et al, 2002), though this is unlikely to affect the data, given the prolonged pathogenesis of the lesions.…”

Structure of Cerebral Arterioles in Mice Deficient in Expression of the Gene for Endothelial Nitric Oxide Synthase

“…[1][2][3] Several determinants apparently contribute to vascular hypertrophy, including increases in arterial pressure, 4 particularly pulse pressure, [5][6][7] sympathetic nerves, 8,9 genetic factors, 3 the reninangiotensin system, 10,11 and the endothelium-derived contracting factor, endothelin. 12 Another determinant that may contribute to vascular hypertrophy during chronic hypertension is nitric oxide (NO).…”