Effects of angiotensin-converting enzyme inhibitors on cerebral vascular structure in chronic hypertension.
Chronic hypertension profoundly alters the function and structure of cerebral blood vessels. Cerebral arterioles undergo remodelling, with a reduction in external diameter and hypertrophy of the vessel wall and a paradoxical increase in distensibility. The primary aim of this review is to consider recent findings in relation to determinants of remodelling, hypertrophy, and altered distensibility and composition of cerebral blood vessels during chronic hypertension, with an emphasis on the renin-angiotensin system. In particular, we highlight studies designed to examine the hypothesis that the effects of angiotensin-converting enzyme (ACE) inhibitors on cerebral vascular structure in stroke-prone spontaneously hypertensive rats (spSHR) may be independent of their effects on reductions in arterial pressure. For example, treatment of spSHR with the ACE inhibitor perindopril attenuates remodelling of cerebral arterioles, even when given in a low dose that only partially normalizes systemic arterial pressure and does not prevent hypertrophy. In contrast, treatment of spSHR with propranolol does not prevent cerebral arteriolar remodelling, even when given in a dose that produces a larger decrease in blood pressure than is achieved with the low dose of perindopril. Results such as these suggest that remodelling of cerebral arterioles during chronic hypertension may be independent of increases in arterial pressure, and instead may depend primarily on increased activity of the renin-angiotensin system. Evidence is also reviewed that suggests that the renin-angiotensin system may not contribute significantly to hypertrophy of cerebral arterioles during chronic hypertension. Rather, hypertrophy appears to depend in large part on increases in arterial pressure and, in particular, its pulsatile component.
Department of Pathology, University of Iowa College of Medicine & Cardiovascular Center, Iowa City 52242, USA. g-baumbach@uiowa.edu
G L
GL
Baumbach
J M
JM
Chillon
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control
D000806:Angiotensin-Converting Enzyme Inhibitors