The blood vessel as a target organ in hypertension: protective effect of perindopril.
The main target organ in untreated arterial hypertension (HTA) is the blood vessel wall (BVW) of the high pressure system (conductance and resistance arteries), which is primarily responsible for vital organ integrity. Three major structural changes develop in the BVW in experimental and human HTA: hypertrophy of the smooth muscle (increased thickness of the media), reduction in the amount of elastin and increased interstitial collagen deposition. The latter two structural changes are responsible for the increased stiffness (reduced compliance) that characterizes the BVW in untreated HTA. Angiotensin II, endothelins, nitric oxide, local growth factors (fibroblast-derived growth factor, platelet-derived growth factor, transforming growth factor-beta) and metalloproteinases are involved in BVW remodelling, and represent potential targets for drug action. Angiotensin-converting enzyme (ACE) inhibitors are particularly suited for such actions via their angiotensin II-, bradykinin- and/or interstitial metalloproteinases-dependent actions. Unfortunately, limited data are available on BVW protection with conventional ACE inhibitors. The new ACE inhibitor perindopril differs from most others in terms of BVW protection. In carefully designed morphometric experiments, perindopril has been shown to reduce vascular smooth muscle hypertrophy and to normalize the elastin:collagen ratio in the BVW of hypertensive rats. It has been shown that perindopril is unique in that respect since isradipine, metoprolol, hydralazine and captopril all failed to normalize the media:lumen ratio in the hypertensive rat. The functional counterpart of these in vitro structural findings obtained with perindopril has been demonstrated in human HTA patients; increased brachial artery diameter and compliance were observed after three weeks of perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)
Plante
G E
GE
Department of Medicine, University of Sherbrooke, Quebec.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D020913:Perindopril; D014655:Vascular Resistance
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril