Influence of antihypertensive therapy with cilazapril and hydrochlorothiazide on the stiffness of the aorta.
The purpose of this study was to examine the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the elastic properties of the aorta. A standard diuretic antihypertensive drug, hydrochlorothiazide, served for comparisons. Increased aortic stiffness leads to a reduction of the buffering windkessel function and is a major component in the pathophysiology of systolic hypertension, inducing an increase in left ventricular afterload and arterial pulsatile stress as well as a decrease in the subendocardial blood supply. Stiffness of arteries increases with age and blood pressure, and depends on the functional elastic structures of the aortic wall. ACE inhibitors have been shown to directly influence elastic properties of peripheral arteries. Seventeen patients with mild to moderate essential hypertension (age 45-67 years) were treated for 3 months double-blind randomized with either cilazapril (C) 5 mg daily (n = 9) or hydrochlorothiazide (HCTZ) 25 mg daily (n = 8). Aortic elastic properties were noninvasively assessed by measurement of pulse wave velocity along the aorta at rest and during isometric handgrip stress. Accelerated pulse wave velocity indicates elevated arterial stiffness and vice versa. A pressure standardized index of aortic cross-sectional distensibility (2 m) was calculated from arterial mean pressure and pulse wave velocity. Compared with pretreatment values, both therapies significantly reduced blood pressure and pulse wave velocity at rest (C: 9.4 +/- 0.9 vs. 7.7 +/- 0.7 m/sec; HcTZ: 8.9 +/- 0.3 vs. 7.8 +/- 0.4 m/sec; means +/- SEM p < 0.05). During isometric stress only C showed a significant decrease in pulse wave velocity (C: 11.3 +/- 0.8 vs. 9.1 +/- 0.8 m/sec; HCTZ: 9.9 +/- 0.5 vs. 9.0 +/- 0.5 m/sec; means +/- SEM p < 0.05). The index 2m at rest and during handgrip increased significantly (p < 0.05) after C but not after HCTZ. With cilazapril we obtained steeper slopes for the treatment-induced reductions in blood pressure and pulse wave velocity for both rest and handgrip stress values. Correlation of the data at rest and during stress revealed a direct relationship between blood pressure and pulse wave velocity. HCTZ linearly extended the relation observed before treatment toward lower values of blood pressure and corresponding pulse wave velocity without changing the relation per se. Cilazapril, in contrast, moved the relation between these variables and decelerated the pulse wave velocities to a greater extent than would have been expected from the corresponding blood pressure reduction (delta approximately 1 m/sec). These results in patients with mild to moderate essential hypertension support the idea that ACE inhibitors, in addition to reducing blood pressure, may exert an additional hemodynamic effect in improving the elastic properties of the aorta.
Breithaupt-Grögler
K
K
Centre for Cardiovascular Pharmacology Mainz-Wiesbaden, Germany.
Leschinger
M
M
Belz
G G
GG
Butzer
R
R
Erb
K
K
de May
C
C
Sinn
W
W
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects*; D017315:Cilazapril / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004548:Elasticity / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017315:Cilazapril