CLINICAL STUDIES
A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study
Yukihito Higashi, MD, PhD*,
Shota Sasaki, MD*,
Keigo Nakagawa, MD*,
Tomohiro Ueda, MD*,
Atsunori Yoshimizu, MD*,
Satoshi Kurisu, MD*,
Hideo Matsuura, MD, PhD*,
Goro Kajiyama, MD, PhD* and
Tetsuya Oshima, MD, PhD
* First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan
Department of Clinical Laboratory Medicine, Hiroshima University School of Medicine, Hiroshima, Japan
Manuscript received February 8, 1999;
revised manuscript received August 24, 1999,
accepted October 18, 1999.
Reprint requests and correspondence: Dr. Yukihito Higashi, Hiroshima University School of Medicine, First Department of Internal Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan yhigashi{at}mcai.med.hiroshima-u.ac.jp
OBJECTIVES
The purpose of this study was to compare the effect of different antihypertensive agents, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretic agents on endothelial function.
BACKGROUND
Endothelial dysfunction is a component of essential hypertension, and various antihypertensive drugs may be able to restore normal function.
METHODS
Forearm blood flow (FBF) was measured in 296 patients with essential hypertension, including 46 untreated subjects using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin (NTG). Forty-seven normotensive subjects were similarly evaluated as control subjects.
RESULTS
The FBF during reactive hyperemia in the 296 hypertensive patients was significantly less than that in age-matched normotensive subjects. The increase in FBF after administration of sublingual NTG was similar in both groups. Systolic and diastolic blood pressures and forearm vascular resistance were greater in the untreated group than in the four treated groups and did not differ with respect to the antihypertensive agent used. The maximal FBF response from reactive hyperemia was significantly greater in the ACE inhibitortreated group than in the group treated with calcium antagonists, beta-blockers, diuretic agents, or nothing (40.5 ± 5.2 vs. 32.9 ± 5.8, 34.0 ± 5.6, 32.1 ± 5.9, and 31.9 ± 5.8 ml/min per 100 ml tissue, p < 0.05, respectively). Reactive hyperemia was similar in the calcium antagonist, beta-blocker, diuretic and untreated groups, and changes in FBF after sublingual NTG administration were similar in all groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of reactive hyperemia in hypertensive patients treated with ACE inhibitors.
CONCLUSIONS
These findings suggest that ACE inhibitors augment reactive hyperemia, an index of endothelium-dependent vasorelaxation, in patients with essential hypertension. This augmentation may be due to increases in NO.
|
Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | ANOVA | = analysis of variance | | FBF | = forearm blood flow | | HDL | = high density lipoprotein | | L-NMMA | = NG-monomethyl-L-arginine | | NO | = nitric oxide | | NTG | = nitroglycerin |
|
This article has been cited by other articles:

|
 |

|
 |
 
R. E. Schmieder, C. Delles, A. Mimran, J. P. Fauvel, and L. M. Ruilope
Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes
Diabetes Care,
June 1, 2007;
30(6):
1351 - 1356.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. A. Ahimastos, A. Lawler, C. M. Reid, P. A. Blombery, and B. A. Kingwell
Brief Communication: Ramipril Markedly Improves Walking Ability in Patients with Peripheral Arterial Disease: A Randomized Trial
Ann Intern Med,
May 2, 2006;
144(9):
660 - 664.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Erzen, P. Gradisek, P. Poredos, and M. Sabovic
Treatment of Essential Arterial Hypertension with Enalapril Does Not Result in Normalization of Endothelial Dysfunction of the Conduit Arteries
Angiology,
March 1, 2006;
57(2):
187 - 192.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Dell'Omo, G. Penno, S. Del Prato, and R. Pedrinelli
Chlorthalidone Improves Endothelial-Mediated Vascular Responses in Hypertension Complicated by Nondiabetic Metabolic Syndrome
Journal of Cardiovascular Pharmacology and Therapeutics,
October 1, 2005;
10(4):
265 - 272.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
D Tousoulis, C Antoniades, E Bosinakou, M Kotsopoulou, C Tsioufis, C Tentolouris, A Trikas, C Pitsavos, and C Stefanadis
Effects of atorvastatin on reactive hyperaemia and the thrombosis-fibrinolysis system in patients with heart failure
Heart,
January 1, 2005;
91(1):
27 - 31.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. F. Harris and K. A. Matthews
Interactions Between Autonomic Nervous System Activity and Endothelial Function: A Model for the Development of Cardiovascular Disease
Psychosom Med,
March 1, 2004;
66(2):
153 - 164.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita
The clinical implications of endothelial dysfunction
J. Am. Coll. Cardiol.,
October 1, 2003;
42(7):
1149 - 1160.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Tousoulis, C. Antoniades, C. Tountas, E. Bosinakou, M. Kotsopoulou, P. Toutouzas, and C. Stefanadis
Vitamin C Affects Thrombosis/ Fibrinolysis System and Reactive Hyperemia in Patients With Type 2 Diabetes and Coronary Artery Disease
Diabetes Care,
October 1, 2003;
26(10):
2749 - 2753.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Yavuz, M. Koc, A. Toprak, I. Akp{iota}nar, A. Velioglu, O. Deyneli, G. Haklar, and S. Akalln
Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients
Journal of Renin-Angiotensin-Aldosterone System,
September 1, 2003;
4(3):
197 - 203.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Kimura, Y. Higashi, K. Hara, K. Noma, S. Sasaki, K. Nakagawa, C. Goto, T. Oshima, M. Yoshizumi, and K. Chayama
PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in Smokers
Hypertension,
May 1, 2003;
41(5):
1106 - 1110.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Enseleit, T.F. Luscher, and F. Ruschitzka
Angiotensin-converting enzyme inhibition and endothelial dysfunction: focus on ramipril
Eur. Heart J. Suppl.,
January 1, 2003;
5(suppl_A):
A31 - A36.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Higashi, S. Sasaki, K. Nakagawa, H. Matsuura, T. Oshima, and K. Chayama
Endothelial Function and Oxidative Stress in Renovascular Hypertension
N. Engl. J. Med.,
June 20, 2002;
346(25):
1954 - 1962.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Higashi, S. Sasaki, K. Nakagawa, M. Kimura, S. Sasaki, K. Noma, H. Matsuura, K. Hara, C. Goto, T. Oshima, et al.
Excess Norepinephrine Impairs Both Endothelium-Dependent and -Independent Vasodilation in Patients With Pheochromocytoma
Hypertension,
February 1, 2002;
39(2):
513 - 518.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-M. Chillon and G. L. Baumbach
Effects of an Angiotensin-Converting Enzyme Inhibitor and a {beta}-Blocker on Cerebral Arteriolar Dilatation in Hypertensive Rats
Hypertension,
June 1, 2001;
37(6):
1388 - 1393.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Higashi, S. Sasaki, K. Nakagawa, H. Matsuura, G. Kajiyama, and T. Oshima
Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function
J. Am. Coll. Cardiol.,
March 1, 2001;
37(3):
863 - 870.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Shaw, J. P. F. Chin-Dusting, B. A. Kingwell, and A. M. Dart
Diurnal Variation in Endothelium-Dependent Vasodilatation Is Not Apparent in Coronary Artery Disease
Circulation,
February 13, 2001;
103(6):
806 - 812.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Duffy, N. Gokce, M. Holbrook, L. M. Hunter, E. S. Biegelsen, A. Huang, J. F. Keaney Jr., and J. A. Vita
Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension
Am J Physiol Heart Circ Physiol,
February 1, 2001;
280(2):
H528 - H534.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Higashi, M. Sanada, S. Sasaki, K. Nakagawa, C. Goto, H. Matsuura, K. Ohama, K. Chayama, and T. Oshima
Effect of Estrogen Replacement Therapy on Endothelial Function in Peripheral Resistance Arteries in Normotensive and Hypertensive Postmenopausal Women
Hypertension,
February 1, 2001;
37(2):
651 - 657.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. H. O'Keefe, M. Wetzel, R. R. Moe, K. Brosnahan, and C. J. Lavie
Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease?
J. Am. Coll. Cardiol.,
January 1, 2001;
37(1):
1 - 8.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|