Acute and long-term effects of angiotensin converting enzyme inhibition on larger arteries and cardiac hypertrophy: mechanical and structural parameters.

UNLABELLED

AIM OF STUDIES: The extent of cardiovascular alterations in hypertension is related quantitatively to the degree of hypertension. However, there is increasing evidence that humoral processes, which are not dependent on blood pressure, are of major importance in these alterations. In particular, angiotensin converting enzyme (ACE) activity seems to be involved. We therefore compared the effects of blood pressure reduction and of acute and long-term ACE inhibition on cardiac hypertrophy, arterial function and morphologic alterations in hypertension.

ACUTE STUDY

To examine the acute effect of ACE inhibition on arterial compliance, we used an experimental model allowing a pressure-volume determination in the carotid artery in situ to assess arterial compliance in normotensive Wistar-Kyoto and spontaneously hypertensive rats. The pressure-volume relationship was determined after an acute, single, oral administration of either placebo or the ACE inhibitor quinapril in doses of 0.3 and 3 mg/kg. Both doses of quinapril produced a similar relaxation of arterial smooth muscle, approximately 80-90% of the maximum relaxation produced by potassium cyanide. LONG-TERM STUDY: We then studied the long-term effects of ACE inhibition compared with those of hydralazine. Four groups of 4-week-old spontaneously hypertensive rats were treated for 4 months with quinapril at 1 or 10 mg/kg per day, hydralazine at 15 mg/kg per day or placebo. Blood pressure, plasma and aortic ACE activity, left ventricular weight and histomorphometric parameters of the thoracic aorta, the renal and the mesenteric arteries were evaluated. We found a marked dissociation between the effects on blood pressure and cardiovascular structural parameters. Whereas both hydralazine and 10 mg/kg quinapril prevented the development of hypertension and aortic hypertrophy in a pressure-dependent manner, only the ACE inhibitor prevented left ventricular hypertrophy and aortic collagen accumulation. These quinapril effects were observed even with a small non-antihypertensive dose (1 mg/kg); the effect on aortic collagen was related to a reduction in aortic but not plasma ACE.

CONCLUSIONS

These results indicate that the acute and long-term effects of ACE inhibitors on arterial function and structure go well beyond their antihypertensive actions and seem to be related to inhibition of tissue ACE. However, while clear effects were observed in the particular arterial segment explored, it may not be valid to extrapolate these findings to other arterial segments.