DOSE OPTIMIZATION STUDY OF ARTERIAL CHANGES ASSOCIATED WITH ANGIOTENSIN CONVERTING ENZYME-INHIBITION IN HYPERTENSION

Background: In treating hypertension the optimal dose of angiotensin converting enzyme (ACE) inhibitor is derived from dose-response curves that relate the quantity of drug taken to the resulting fall in blood pressure; the blood pressure fall reflects a decrease in vascular resistance and hence, a degree of arteriolar vasodilation. However, ACE inhibition dilates not only the small arteries but also the larger calibre arteries, which increases compliance. Given the differences in structure and function of large and small arteries, the optimal drug dose for a given vessel may differ according to the size and structure of the vessel. Dose-response effects in clinical studies: Clinical studies indicate that in the brachial artery territory, larger doses are required to obtain arterial dilation than to produce a decrease in vascular resistance. In the aorta, an improvement in arterial compliance and distensibility is governed both by the fall in blood pressure and the drug dose. Finally, for the femoral artery, the degree of arterial dilation is influenced markedly only by the drug dose. Application to treatment: An understanding of the drug dose required to produce a given change in the hypertensive arterial system may have important implications for the control of blood pressure. For a given mean arterial pressure, systolic blood pressure is lower and diastolic blood pressure higher when aortic compliance is increased, a haemodynamic change commonly seen following ACE inhibition. Recent double-blind studies have shown that ACE inhibitors produced a more pronounced decrease in systolic than diastolic blood pressure. Conclusion: These findings indicate that the optimum doses required to improve the arterial wall in large arteries must be evaluated by long-term antihypertensive therapy.