BLOOD PRESSURE
1992; 1: 187
LETTER TO THE EDITOR
Blood Press Downloaded from informahealthcare.com by University of Adelaide on 12/10/14 For personal use only.
Aortic Compliance in Hypertension-Effects of Cilazapril and Hydrochlorothiazide Can Be Distinguished Sir, Reduced compliance of the aorta and the large elastic arteries is a major component in the pathophysiology of hypertension. The buffering function of the arterial system (windkessel) mainly depends on these vessels whereas large arteries of the muscular type are not involved [I]. Though any reduction in blood pressureby ways of physical law-improves compliance [2], it has been suggested that ACE inhibitors could lead to an additional reduction in vascular stiffness [I, 3,4]. These findings led us to investigate whether chronic treatment with an ACE inhibitor, as compared to antihypertensive therapy with a diuretic, might improve aortic compliance thus enhancing the effects induced by mere blood pressure reduction. Seventeen patients aged from 45 to 67 years with mild to moderate essential hypertension participated in a randomized double-blind study. Following a 2-week placebo run-in period, 9 received the ACE inhibitor cilazapril5 mg daily and 8 the diuretic hydrochlorothiazide (HCTZ) 25 mg daily for 3 months each. Mean compliance between the carotid and femoral arteries was derived from pulse wave velocity (PWV) recorded by sphygmography [ 5 ] . A high PWV indicates a low aortic compliance and vice versa. Before active treatment there were no statistically significant differences in mean (SEM) diastolic blood pressure (cilazapril: 95 (3), HCTZ 102 (4) mmHg) or PWV (cilazapril9.4 (0.9), HCTZ 8.9 (0.3) m/s) between diastolic blood pressure (rnrnHg)
the two groups. Both treatments reduced diastolic blood pressure and PWV significantly ( p < 0.05) (Fig. 1). In spite of the greater blood pressure lowering effect of the diuretic, the improvement of aortic compliance appeared to be higher with the ACE inhibitor. An intention-to-treat analysis relating the percentage decrease in PWV to that in blood pressure revealed a distinction between the two treatments (Wilcoxon test: p = 0.075, t-test p < 0.05). These results in this small number of middle-aged patients suggest that cilazapril beyond its well known antihypertensive efficacy [6, 71 also directly improves aortic compliance. This might be of therapeutic relevance and result in further benefit for the patient. Dr. med. Kerstin Breithaupt Monika Leschinger Dr. med. Christian de Mey Prof. Dr. med. Gustav G . Belz
REFERENCES 1. Perret F, Mooser V, Hayoz D, et al. Evaluation of arterial
2.
3.
4. 5.
compliance-pressure curves. Effects of antihypertensive drugs. Hypertension 1991; 18 (Suppl 11): 1173-83. Bramwell JC, Downing AC, Hill AV. The effect of blood pressure on the extensibility of the human artery. Heart 1923; 10: 289-300. Watkins RW, Sybertz EJ, Antonellis A, Pula K. Effects of spiraprilic acid, an angiotensin converting enzyme inhibitor, on large artery compliance in anesthetized dogs. Arch Int Pharmacodyn Ther 1987; 290: 222-34. Benetos A, Santoni JP, Safar ME. Vascular effects of intravenous infusion of the angiotensin converting enzyme inhibitor perindoprilat. J Hypertens 1990; 8: 8 19-26. Breithaupt K, Belz GG, Sinn W. Non-invasive assessments of compliance of the aortic windkessel in man derived from pulse pressure/storage volume ratio and from pulse wave velocity. Clin Physiol Biochem 1992; 9: 18-25. Szucs T. Cilazapril-a review. Drugs 1991; 41 (Suppl 1): 18-24. Belz GG, Breithaupt K, Erb K, Kleinbloesem CH, Wolf GK. Influence of the angiotensin converting enzyme inhibitor cilazapril, the beta-blocker propranolol and their haemodynamics in hypertension. J Hypertens 1989; 7: 8 17-24.
I 6. 7.
-2
c
Submitted July 13, 1992 Address for correspondence:
I
1 -
~
Fig. I. Relation between decrease in diastolic blood pressure and pulse wave velocity after three months 5 mg cilazapril or 25 mg hydrochlorothiazide daily (means, SEM, 3 h after drug intake).
Kerstin Breithaupt Zentrum fur Kardiovaskulare Pharmakologie Mathildenstrasse 8 D-6500 Mainz Germany
1992; 1: 187
LETTER TO THE EDITOR
Blood Press Downloaded from informahealthcare.com by University of Adelaide on 12/10/14 For personal use only.
Aortic Compliance in Hypertension-Effects of Cilazapril and Hydrochlorothiazide Can Be Distinguished Sir, Reduced compliance of the aorta and the large elastic arteries is a major component in the pathophysiology of hypertension. The buffering function of the arterial system (windkessel) mainly depends on these vessels whereas large arteries of the muscular type are not involved [I]. Though any reduction in blood pressureby ways of physical law-improves compliance [2], it has been suggested that ACE inhibitors could lead to an additional reduction in vascular stiffness [I, 3,4]. These findings led us to investigate whether chronic treatment with an ACE inhibitor, as compared to antihypertensive therapy with a diuretic, might improve aortic compliance thus enhancing the effects induced by mere blood pressure reduction. Seventeen patients aged from 45 to 67 years with mild to moderate essential hypertension participated in a randomized double-blind study. Following a 2-week placebo run-in period, 9 received the ACE inhibitor cilazapril5 mg daily and 8 the diuretic hydrochlorothiazide (HCTZ) 25 mg daily for 3 months each. Mean compliance between the carotid and femoral arteries was derived from pulse wave velocity (PWV) recorded by sphygmography [ 5 ] . A high PWV indicates a low aortic compliance and vice versa. Before active treatment there were no statistically significant differences in mean (SEM) diastolic blood pressure (cilazapril: 95 (3), HCTZ 102 (4) mmHg) or PWV (cilazapril9.4 (0.9), HCTZ 8.9 (0.3) m/s) between diastolic blood pressure (rnrnHg)
the two groups. Both treatments reduced diastolic blood pressure and PWV significantly ( p < 0.05) (Fig. 1). In spite of the greater blood pressure lowering effect of the diuretic, the improvement of aortic compliance appeared to be higher with the ACE inhibitor. An intention-to-treat analysis relating the percentage decrease in PWV to that in blood pressure revealed a distinction between the two treatments (Wilcoxon test: p = 0.075, t-test p < 0.05). These results in this small number of middle-aged patients suggest that cilazapril beyond its well known antihypertensive efficacy [6, 71 also directly improves aortic compliance. This might be of therapeutic relevance and result in further benefit for the patient. Dr. med. Kerstin Breithaupt Monika Leschinger Dr. med. Christian de Mey Prof. Dr. med. Gustav G . Belz
REFERENCES 1. Perret F, Mooser V, Hayoz D, et al. Evaluation of arterial
2.
3.
4. 5.
compliance-pressure curves. Effects of antihypertensive drugs. Hypertension 1991; 18 (Suppl 11): 1173-83. Bramwell JC, Downing AC, Hill AV. The effect of blood pressure on the extensibility of the human artery. Heart 1923; 10: 289-300. Watkins RW, Sybertz EJ, Antonellis A, Pula K. Effects of spiraprilic acid, an angiotensin converting enzyme inhibitor, on large artery compliance in anesthetized dogs. Arch Int Pharmacodyn Ther 1987; 290: 222-34. Benetos A, Santoni JP, Safar ME. Vascular effects of intravenous infusion of the angiotensin converting enzyme inhibitor perindoprilat. J Hypertens 1990; 8: 8 19-26. Breithaupt K, Belz GG, Sinn W. Non-invasive assessments of compliance of the aortic windkessel in man derived from pulse pressure/storage volume ratio and from pulse wave velocity. Clin Physiol Biochem 1992; 9: 18-25. Szucs T. Cilazapril-a review. Drugs 1991; 41 (Suppl 1): 18-24. Belz GG, Breithaupt K, Erb K, Kleinbloesem CH, Wolf GK. Influence of the angiotensin converting enzyme inhibitor cilazapril, the beta-blocker propranolol and their haemodynamics in hypertension. J Hypertens 1989; 7: 8 17-24.
I 6. 7.
-2
c
Submitted July 13, 1992 Address for correspondence:
I
1 -
~
Fig. I. Relation between decrease in diastolic blood pressure and pulse wave velocity after three months 5 mg cilazapril or 25 mg hydrochlorothiazide daily (means, SEM, 3 h after drug intake).
Kerstin Breithaupt Zentrum fur Kardiovaskulare Pharmakologie Mathildenstrasse 8 D-6500 Mainz Germany
