EFFECTS OF ANTIHYPERTENSIVE THERAPY ON MECHANICS OF CEREBRAL ARTERIOLES IN RATS

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 1,244 +/- 101 and 1,388 +/- 59-mu-m2, respectively, compared with 1,405 +/- 95-mu-m2 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-mu-m for cilazapril versus 91 +/- 3-mu-m for hydralazine compared with 107 +/- 3-mu-m 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.