VASCULAR REMODELING IN SYSTEMIC HYPERTENSION

It is now well accepted that treatment of hypertension must extend bey ond the mere control of blood pressure. Among the objectives ''beyond blood pressure control'' is the remodeling of resistance and complianc e vessels that have usually undergone a process of hypertrophy and/or hyperplasia. Salutary vascular remodeling by antihypertensive treatmen t not only implies structural changes of the vascular wall, but also f unctional improvements, including diminished contractile responses to endogenous vasoconstrictors and enhanced relaxation to endogenous vaso dilators. We have treated spontaneously hypertensive rats with the ang iotensin-converting enzyme (ACE) inhibitors zabicipril, perindopril, a nd ramipril at antihypertensive and sub-antihypertensive doses and hav e analyzed vascular morphology and function. Chronic oral treatment wa s begun before hypertension developed (prevention study). Remodeling o f mesenteric vessels with, inter alia, a reduction of the media:lumen ratio was achieved by antihypertensive doses of the drugs. Further, va scular function was improved not only after high-dose, but also after low-dose ACE inhibitor treatment, as tested in the aortic vessels: an inhibition of vascular ACE was associated with attenuated vasoconstric tor responses to norepinephrine and enhanced dilator responses to acet ylcholine in addition, low and high doses significantly increased aort ic cyclic guanosine monophosphate (cGMP) content, suggesting an improv ed vasodilator capacity. Our data demonstrate that improvements of vas cular function can be achieved by ACE inhibitors, independently of str uctural changes and of the antihypertensive action exerted by these dr ugs.