Effects of Antihypertensive Treatment on Composition of Cerebral Arterioles

Hajdu, Michael A.
Heistad, Donald D.
Ghoneim, Shams
Baumbach, Gary L.

University of Iowa College of Medicine, Departments of Pathology, Internal Medicine, and Pharmacology, Center on Aging and the Cardiovascular Center, and the Veterans Administration Medical Center, Iowa City, Iowa.

Address for correspondence: Michael A. Hajdu, PhD, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242.

Supported by funds from the Iowa Affiliate of the American Heart Association; National Institutes of Health grants HL-22149, NS-24621, HL-16066, HL-14230, HL-14388, and HL-07121-15; Medical Investigatorship and funds from the Veterans Administration; and by funds from F. Hoffmann-La Roche and Co. G.L.B. is the recipient of an Established Investigator Award from the American Heart Association. This manuscript from the University of Iowa was sent to Jean-Paul Clozel, Guest Editor, for review by expert referees, for editorial decision, and for final disposition.

Hypertension 18(4):p II-21, October 1991.

Treatment of chronic hypertension with cilazapril, but not hydralazine, attenuates changes in distensibility of cerebral arterioles that occur in stroke-prone spontaneously hypertensive rats (SHRSPs). In this study, effects of antihypertensive treatment on composition of cerebral arterioles was determined in SHRSPs. Cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or hydralazine (18 mg/kg/day) was begun when rats were 3 months of age. Both cilazapril and hydralazine reduced systolic arterial pressure in SHRSPs (from 199±6 to 122±7 mm Hg for cilazapril versus 143±5 mm Hg for hydralazine [mean±SEM];p<0.05). Cerebral arterioles were fixed in vivo, and the cross-sectional area of the vessel wall was measured histologically. In SHRSPs, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to values obtained in Wistar-Kyoto (WKY) rats. Thus, both cilazapril and hydralazine prevented hypertrophy of cerebral arterioles in SHRSPs. Composition of the arteriolar wall was determined with point counting stereology. Cerebral arterioles in SHRSPs contained significantly more smooth muscle and elastin than in WKY rats (1,294 ±157 versus 853±88 μm², respectively, for smooth muscle and 148±13 versus 108±7 μm², respectively, for elastin). After treatment with the ACE inhibitor, the amount of smooth muscle (920±40 μm²) and elastin (120±8 μm²) in cerebral arterioles in SHRSPs was similar to that in WKY rats. Treatment with hydralazine was effective in preventing increases in elastin (128 ±14 μm²) and in attenuating increases in smooth muscle (1,008±18 fim1). The ratio of nondistensible (collagen, basement membrane) to distensible (smooth muscle, elastin, endothelium) components was greater in SHRSPs than in WKY rats. The ratio was normal in SHRSPs after treatment with cilazapril but not hydralazine. Thus, the ACE inhibitor, but not hydralazine, prevented changes in the relative composition of cerebral arterioles in SHRSPs. We speculate that changes in relative composition of cerebral arterioles may explain, in part, different effects of antihypertensive treatment on vascular mechanics.