Functional and structural effects of ACE inhibitors on the cardiovascular system

There is considerable interest in the ability of angiotensin-converting enzyme (ACE) inhibitors not only to lower blood pressure, but also to reverse hypertension-induced remodelling of the circulation. Recently published data would suggest that treatment of spontaneously hypertensive rats from an early age with ACE inhibitors will prevent the development of the expected changes in the resistance vessels as the animals age and that withdrawal of treatment is followed by a lag period before the blood pressure rises. Such findings appear to be contrary to those obtained with other hypertensive drugs where morphological changes are not as effectively attenuated and blood pressure rises rapidly after withdrawal of treatment. There is some evidence for a relationship between the efficacy of ACE inhibitors in this area and lipid solubility. This raises the possibility that the mechanism at work is related to the inhibition of tissue-located renin-angiotensin systems both in vascular smooth muscle and elsewhere, possibly in the central nervous system. An overall review of the literature indicates that treatment of spontaneously hypertensive rats with ACE inhibitors can result in prolonged reduction of blood pressure, even after treatment is withdrawn. Comparisons with other treatments suggest that it is easier to reduce blood pressure than to reverse vascular structure. However, achieving a reversal in morphological changes in resistance vessels as well as controlling blood pressure may be important for reducing the mortality from ischaemic heart disease. ACE inhibitors may have a direct effect on reversal of vascular structure, but other sites of action may also be important in this aspect of their action.