Different Effect of Antihypertensive Drugs on Conduit Artery Endothelial Function

Abstract

Abstract-To compare the effect of antihypertensive drugs on endothelium-dependent vasodilation in the peripheral conduit arteries of patients with essential hypertension, in a prospective, randomized, parallel group study, endothelial function was assessed in 168 hypertensive patients before and after 6-month treatment with randomly assigned nifedipine GITS (30 to 60 mg, nϭ28), amlodipine (5 to 10 mg, nϭ28), atenolol (50 to 100 mg, nϭ29), nebivolol (5 to 10 mg, nϭ28), telmisartan (80 to 160 mg, nϭ29), and perindopril (2 to 4 mg, nϭ28). If necessary, hydrochlorothiazide (25 mg) was added to each compound. We evaluated brachial artery flow-mediated, endothelium-dependent dilation (high-resolution ultrasound) compared with endothelium-independent response to glyceryl trinitrate (25 g/s). Brachial artery diameter was measured by automatic computerized analysis. Forty healthy subjects were evaluated as a control group. Oxidative stress production was evaluated by measuring plasma malondialdehyde and plasma lipoperoxides; plasma antioxidant capacity was assessed as ferric-reducing antioxidant power. Hypertensive patients showed a significantly (PϽ0.01) lower flow-mediated dilation (5.2Ϯ1.9%) as compared with healthy control subjects (7.1Ϯ2.6%). Response to glyceryl trinitrate was similar in control subjects and patients. At baseline, blood pressure, diameter, flow-mediated dilation, and response to glyceryl trinitrate were similar in the different treatment groups. All treatments similarly reduced blood pressure, but only perindopril increased flow mediated dilation (from 5.1Ϯ2 to 6.4Ϯ2.4%; PϽ0.01) without modifying the response to glyceryl trinitrate. Perindopril but also telmisartan nifedipine and amlodipine reduced oxidative stress and increased plasma antioxidant capacity. In patients with essential hypertension, ACE inhibitors appear to be the only compounds able to improve conduit artery endothelium-dependent vasodilation.

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

“…The question naturally arises as to why spironolactone failed to improve endothelial function in our study patients, despite significant reductions in blood pressure. This finding is interesting as virtually all other antihypertensives improve endothelial function, although the effect of some antihypertensives may be greater than that of others because of possible blood pressure-independent effects on endothelial function [31][32][33][34][35]. We can only speculate that the blood pressure-lowering benefit on endothelial function was prevented as a result of several possible factors, as follows.…”

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

“…Ghiadoni et al 7 observed that ACEI, but not ARB, improved endothelial function; whereas Koh et al 26 reported that both ACEI and ARB increased FMD. The beneficial effect of ACEI on endothelial vasodilator function is reportedly mediated by a bradyki- nin-dependent pathway where ACEI directly inhibits bradykinin degradation by ACE.…”

“…Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II (Ang II) type 1 receptor antagonists (ARB) are essential drugs for such patients, 5 and have been reported to restore decreased endothelial function by improving NO availability. 6 However, it is still controversial whether improvement of endothelial function is an effect of the RAS inhibitor class because several investigators were unable to observe such an effect for ARB 7 in spite of beneficial effects seen for other classes of antihypertensives. 8 Basic research has clearly demonstrated that the Ang II-mediated signal transduction pathway induces inflammation and oxidative stress.…”

Drug Treatment of Hypertension: Focus on Vascular Health

“…In patients with essential hypertension, treatment with cizalapril for 2 years and lisinopril for 3 years improved vascular responses to acetylcholine in the subcutaneous microcirculation 4,[116][117][118] . Furthermore, within the peripheral circulation, perindopril, ramipril, quinapril and the perindopril-indapamide combination improve flowmediated dilatation, which most likely relates to increased NO bioavailability and prevention of angiotensin-II induced oxidative stress 4,35,37,115,[119][120][121] . ACE inhibitors may also potentiate bradykinin activity, which stimulates release of NO, PGI 2 and EDHF from the endothelium 22 .…”