Vascular and cardiac protection by ramipril in spontaneously hypertensive rats: prevention versus regression study

The effect of chronic oral treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril at antihypertensive and sub-antihypertensive doses, on vascular morphology and function as well as left ventricular hypertrophy (LVH) and cardiac capillary length density was investigated in spontaneously hypertensive rats (SHR). Treatment was commenced before hypertension developed (prevention study) or in adult animals with established hypertension (regression study). In both studies, high-dose ramipril reduced ACE activity in plasma, heart and aorta, normalised blood pressure, and prevented LVH or caused regression of LVH. Low-dose ramipril did not prevent the development of hypertension or LVH, but caused an increase in cardiac capillary length density. In adult hypertensive animals, low-dose ramipril did not reduce blood pressure but caused regression of LVH. In both studies, vascular function as tested in the aortic vessels was improved not only after high- but also after low-dose ACE inhibitor treatment: an inhibition of vascular ACE was associated with attenuated vasoconstrictor responses to norepinephrine and enhanced dilator responses to acetylcholine and bradykinin. A reduction of vascular hypertrophy/hyperplasia in the mesenteric vessels was achieved by the antihypertensive dose of ramipril in the prevention but not the regression study. Our data demonstrate that an improvement of vascular function in SHR can be achieved by chronic ACE inhibition with ramipril independently of structural changes and of the antihypertensive action exerted by the drug. LVH was reduced even at a sub-antihypertensive dose of ramipril in the regression but not the prevention study. In the prevention study, however, low-dose ramipril, like high-dose ramipril, was able to protect the heart by preventing cardiac microvascular rarefaction.