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.

OBJECTIVES The purpose of this study was to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the calcium antagonist amlodipine on endothelial function before and after 2, 4, 8, 12, 24 and 48 weeks of treatment. BACKGROUND There are limited data on whether and how long endothelial function is improved after initiation of ACE inhibitor treatment and how the grade of endothelial function further progresses after improvement of endothelial dysfunction in patients with essential hypertension. METHODS The forearm blood flow (FBF) was measured in 25 patients with essential hypertension and in 25 normotensive subjects by using strain-gauge plethysmography during reactive hyperemia (RH) (280 mm Hg for 5 min) and after sublingual administration of nitroglycerin (NTG, 0.3 mg). RESULTS The FBF of patients with essential hypertension during RH was significantly less than that of normotensive subjects. The increase in FBF after sublingual NTG was similar in both groups. Both imidapril (n = 13) and amlodipine (n = 12) significantly reduced systolic blood pressure and diastolic after eight weeks of treatment from the pretreatment values. Forearm vascular resistance was significantly decreased after two weeks of treatment. Imidapril significantly augmented RH after 12 weeks of treatment from the pretreatment values (31.6 +/- 5.7 to 38.2 +/- 6.0 m/min per 100 ml tissue, p < 0.05), whereas amlodipine did not alter RH for each treatment period. The ability of imidapril to improve RH was maintained throughout the 48-week treatment period. There was no significant difference in RH at 12, 24 and 48 weeks. The increase in FBF after sublingual administration of NTG was similar in all treatment periods for the two groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of RH in hypertensive patients treated with imidapril. CONCLUSIONS These findings suggest that the ACE inhibitor imidapril augments RH after 12 weeks of treatment in patients with essential hypertension and that this ACE inhibitor-induced augmentation of RH may be due to an increase in NO.

[1]  T. Lüscher,et al.  Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. , 1990, Circulation.

[2]  J. Webster,et al.  The effect of antihypertensive therapy on responsiveness to local intra‐arterial NG-monomethyl‐L-arginine in patients with essential hypertension , 1994, Journal of hypertension.

[3]  G. Kajiyama,et al.  Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. , 1999, Circulation.

[4]  L. Ghiadoni,et al.  Effects of angiotensin converting enzyme inhibition on endothelium‐dependent vasodilatation in essential hypertensive patients , 1998, Journal of hypertension.

[5]  P. Vanhoutte,et al.  Endothelium‐derived relaxing and contracting factors , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[7]  M. Omata,et al.  Nitric oxide release from kidneys of hypertensive rats treated with imidapril. , 1996, Hypertension.

[8]  A. Quyyumi,et al.  Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. , 1990, The New England journal of medicine.

[9]  P. Vanhoutte,et al.  Endothelium-dependent effects of converting-enzyme inhibitors. , 1993, Journal of cardiovascular pharmacology.

[10]  T. Lüscher.  Imbalance of endothelium-derived relaxing and contracting factors. A new concept in hypertension? , 1990, American journal of hypertension.

[11]  E. Schiffrin,et al.  Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients. , 1995, Hypertension.

[12]  M. Clozel,et al.  Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats. , 1990, Hypertension.

[13]  T. Ogihara,et al.  Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension. , 1997, Hypertension.

[14]  G. Kajiyama,et al.  Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension. , 1998, Hypertension.

[15]  P. Vanhoutte,et al.  Inhibition of the angiotensin converting enzyme by perindoprilat and release of nitric oxide. , 1995, American journal of hypertension.

[16]  A. Mimran,et al.  Contrasting effect of antihypertensive treatment on the renal response to L-arginine. , 1995, Hypertension.

[17]  M. Daemen,et al.  Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. , 1991, Circulation research.

[18]  H. Drexler,et al.  Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans. , 1997, Circulation.

[19]  M. Creager,et al.  Effect of captopril and enalapril on endothelial function in hypertensive patients. , 1994, Hypertension.

[20]  P. Vanhoutte,et al.  Endothelium-derived hyperpolarizing factor and endothelium-dependent relaxations. , 1993, American journal of respiratory cell and molecular biology.

[21]  S. Moncada,et al.  EFFECTS OF ENDOTHELIUM-DERIVED NITRIC OXIDE ON PERIPHERAL ARTERIOLAR TONE IN MAN , 1989, The Lancet.

[22]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[23]  G. Kajiyama,et al.  Aging and severity of hypertension attenuate endothelium-dependent renal vascular relaxation in humans. , 1997, Hypertension.

[24]  G. Kajiyama,et al.  Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension. , 1999, Hypertension.

[25]  M. Sugimachi,et al.  Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Different responses to acetylcholine and substance P. , 1995, Hypertension.

[26]  Carter Vb,et al.  The power of words. , 1951, Lancet.

[27]  G. Kajiyama,et al.  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. , 2000, Journal of the American College of Cardiology.

[28]  P. Vanhoutte,et al.  Endothelium-derived hyperpolarizing factor. , 1996, Clinical and experimental pharmacology & physiology.

[29]  L. Ghiadoni,et al.  Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. , 1998, Circulation.

[30]  P. Vanhoutte.  Endothelium and Control of Vascular Function State of the Art Lecture , 1989, Hypertension.