Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Indapamide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed1992

Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: results of a double-blind multicenter study versus atenolol.

A 3-month double-blind multicenter trial compared the efficacy and safety of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor, with atenolol in mild-to-moderate essential hypertension. A total of 190 patients, 49 of whom were diabetic, entered the perindopril-atenolol comparison. Of these, 163 had been previously treated and had a 4-week run-in period on placebo; 27 had previously been untreated and received placebo for 2 weeks. At entry, all patients who had a supine diastolic blood pressure (DBP) of 95-115 mm Hg were randomized to receive perindopril 2 mg or atenolol 25 mg, once daily. Patients were assessed at 2 weekly intervals for the first month and then monthly for 2 more months. If supine DBP was greater than 90 mm Hg, treatment was increased by stepwise doubling of dose up to 8 mg perindopril or 100 mg atenolol once daily, and later by the addition of hydrochlorothiazide 25 mg, (indapamide 2.5 mg in diabetic patients) once daily. The two groups were homogeneous prior to treatment except for supine and erect heart rate, which were higher in the perindopril group than in the atenolol group (p less than 0.05). Mean supine DBP was 101.1 +/- 0.6 mm Hg in the perindopril group (n = 94) and 99.9 +/- 0.6 mm Hg in the atenolol group (n = 96). After 3 months' active treatment, 74% of patients in the perindopril group achieved a supine DBP of less than or equal to 90 mm Hg and 73% of patients in the atenolol group achieved the same goal. Monotherapy controlled supine DBP in 67% of the perindopril group and 63% of the atenolol group. The decrease in supine DBP was not significantly different between the two groups (-12.9 +/- 0.9 versus -14.7 +/- 0.9 mm Hg) but the decrease in erect DBP was lower in the perindopril group (-10.3 +/- 0.9 versus - 13.4 +/- 1.0 mm Hg, p less than 0.02). Heart rate was reduced in the atenolol group (p less than 0.001). Sixteen patients withdrew from the study; nine were attributed to adverse events, two in the perindopril group and seven, including one death, in the atenolol group. Cough was spontaneously reported by 13% patients of the perindopril group and 1% patients of the atenolol group. In 5% of the perindopril cases this was mild and associated with upper respiratory tract infection. The nature and incidence of other symptoms were similar with both drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Inhibition of the Cl-/NaCO3- anion exchanger by xipamide in human red blood cells.

The mechanism of action of classical loop diuretics of the 2- or 3-amino-5-sulfamoylbenzoic acid and (aryloxy)acetic acid families involves competition with chloride for a common site on the (Na+, K+, 2Cl-) co-transport system. However this is not the mechanism of action of some high-ceiling diuretics like muzolimine, MK 473, xipamide, indapamide and clopamide, which are not carboxylic acids. We evaluated three of these latter diuretics (xipamide, muzolimine and clopamide) for their inhibitory effects on five ion transport systems in human red blood cells: (i) Cl(-)-dependent (Na+, K+) co-transport, (ii) (NaCO3-/Cl-) anion exchanger, (iii) (Cl-, K+) co-transport, (iv) Na+, K+ pump and (v) Na+: Li+ counter-transport; and on one ion channel the Ca2+-dependent, K+ channel. All erythrocyte transport pathways were resistant to the three diuretics studied (IC50 of 10(-3) M or higher) with one remarkable exception, the (NaCO3-/Cl-) anion exchanger. This transport system was inhibited by xipamide (IC50 of 2.5 +/- 0.4 X 10(-5) M, mean +/- S.D. of five experiments) and less potently by muzolimine (IC50 of 1.1 +/- 0.3 X 10(-4) M, mean +/- S.D. of three experiments). Clopamide only inhibited the anion exchanger at high concentrations (IC50 of about 10(-3) M). Xipamide, the most potent diuretic in this test, was at least one order of magnitude more active than furosemide, ethacrynic acid, hydrochlorothiazide and amiloride. Inhibition of the anion carrier could be involved in the diuretic action (inhibition of CO2-stimulated NaCl absorption in the TAL) and/or in the antihypertensive action (inhibition of net NaCO3- influx and secondarily of Ca2+ influx through Na+: Ca2+ exchange in vascular smooth muscle cells of xipamide).

Bicarbonates↗
PubMed1991

Diuretics modify [Arg8]vasopressin-stimulated cAMP but not atrial natriuretic peptide-stimulated cGMP formation in renal cells.

The present study was undertaken to examine whether sulfonamide-derived diuretics affect [Arg8]vasopressin (AVP)-stimulated or atrial natriuretic peptide (ANP)-stimulated cyclic nucleotide formation in cells cultured from rat or dog kidney. In rat renal cells, all four sulfonamide-derived diuretics examined significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations of 10(-4) and 10(-3) M, while basal cAMP formation was unchanged by the diuretics. When cells were stimulated with 10(-7) M AVP, low ceiling diuretics (indapamide and trichlormethiazide) did not suppress cAMP formation, while high ceiling diuretics (furosemide and azosemide) significantly suppressed cAMP formation at concentrations of 10(-4) and 10(-3) M. The suppressive effect of the diuretics on AVP-stimulated cAMP formation in vitro paralleled the reported diuretic potency of the agents in vivo. In dog renal cells, all four diuretics significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations from 10(-6) to 10(-5) M, while these diuretics did not change basal cAMP levels. High ceiling diuretics suppressed 10(-7) M AVP-stimulated cAMP formation, whereas low ceiling diuretics did not. The difference in effective doses between rats and dogs seems to be consistent with the species difference observed in vivo. None of the diuretics affected basal levels of intracellular cGMP or ANP-stimulated cGMP formation in cultured rat renal cells. In addition to the inhibition of the Na/K/Cl co-transporter, it is suggested that most sulfonamide-derived diuretics act, at least in part, by inhibiting the actions of AVP.

Animals↗
PubMed1986

Differential effects of diuretics on eicosanoid biosynthesis.

The selective influences of hydrochlorothiazide (HCT), furosemide (FUR), spironolactone (SPI) and indapamide (IND) on arachidonic acid (AA) metabolism were assessed in sheep seminal vesicle and in human platelet microsomes. All four compounds augmented the synthesis of prostaglandins (PGs) D2 (HCT,FUR), E2 (SPI) and I2 (FUR,IND), probably through facilitated reorientation of endoperoxide biotransformation. With the exception of HCT, the other drugs also suppressed the production of thromboxane A2 (IND greater than SPI greater than FUR); lipoxygenase formation of hydroxyeicosatetraenoic acid was also enhanced by SPI and IND. The antihypertensive efficacy of these diuretics could, in part, be related to their selective effects on AA metabolism which favor the net formation of depressor PGs.

Animals↗
PubMed1993

Optimization of the high-performance liquid chromatrographic separation of a mixture of natural and synthetic corticosteroids.

Systematic optimization of the HPLC separation of a mixture of natural and synthetic corticosteroids was carried out for screening purposes. The method involves binary, ternary or quaternary mixtures containing water, methanol, acetonitrile and tetrahydrofuran. It was possible to separate thirteen out of fourteen corticosteroids contained in a sample in about 26 min, with a 5-microns Hypersil-C18 (250 mm x 4.6 mm I.D.) column thermostated at 30 degrees C, using a mobile phase composed of water-tetrahydrofuran (72:28, v/v). This separation was not improved using other C8 or C18 columns. The effect of temperature on the separation of these compounds was also studied. Calibration graphs were established for each corticosteroid up to 8 micrograms/ml using indapamide as internal standard. The detection limits were in the range 0.02-0.14 ng. The optimized method was applied to urine samples spiked with corticosteroids and showed potential for future applications.

Acetonitriles↗
PubMed1992

A novel loop diuretic, torasemide, inhibits thromboxane A2-induced contraction in the isolated canine coronary artery.

We examined the effect of a novel antihypertensive diuretic, torasemide, on the vasoconstriction induced by TXA2 in the isolated canine coronary artery. Carbocyclic thromboxane A2 (CTA2), a stable analogue of the potent coronary vasoconstrictor thromboxane A2, exhibited a slow onset and progressive contraction of isolated canine coronary arteries at 2 x 10(-8) M. Torasemide (10(-7) approximately 10(-4) M) elicited a dose-dependent vasodilating action in the isolated canine coronary arteries contracted by CTA2, whereas indapamide or furosemide had little effect on this preparation. The maximum vasodilating response to torasemide was 45 +/- 12% of vasodilating effect induced by 10(-4) M papaverine. These results suggest that torasemide is a promising antihypertensive agent with a coronary protective effect.

Animals↗
PubMed2006

Rationale and design of the AdRem study: evaluating the effects of blood pressure lowering and intensive glucose control on vascular retinal disorders in patients with type 2 diabetes mellitus.

The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2 factorial randomized controlled trial with an ACE inhibitor-diuretic combination (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type 2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal photographs of both eyes. These are taken within 3 months after randomization in ADVANCE (baseline), at the biennial and at the final visit. The primary outcome is progression of two or more steps in ETDRS classification. Secondary outcomes include progression of retinal vascular lesions and distortion of retinal vascular geometry. Retinal photographs are made on film and digitized at a central laboratory. The AdRem study uses fully digitized quality control and grading. Between August 2002 and January 2004 1978 patients were included in the AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the strict AdRem quality requirements. Publication of the results is expected in early 2008. The AdRem study is designed to provide reliable evidence on the effects of intensive glucose control and blood pressure lowering on both diabetic retinopathy and abnormalities of retinal vasculature in patients with type 2 diabetes mellitus.

Antihypertensive Agents↗
PubMed2006

Fast gas chromatographic/mass spectrometric determination of diuretics and masking agents in human urine: Development and validation of a productive screening protocol for antidoping analysis.

An analytical procedure was developed for the fast screening of 16 diuretics (acetazolamide, althiazide, amiloride, bendroflumethiazide, bumetanide, canrenoic acid, chlorthalidone, chlorthiazide, clopamide, ethacrynic acid, furosemide, hydrochlorthiazide, hydroflumethiazide, indapamide, triamterene, trichlormethiazide) and a masking agent (probenecid) in human urine. The whole method involves three analytical steps, including (1) liquid/liquid extraction of the analytes from the matrix, (2) their reaction with methyl iodide at 70 degrees C for 2 h to form methyl derivatives, (3) analysis of the resulting mixture by fast gas chromatography/electron impact mass spectrometry (fast GC/EI-MS). The analytical method was validated by determining selectivity, linearity, accuracy, intra and inter assay precision, extraction efficiencies and signal to noise ratio (S/N) at the lowest calibration level (LCL) for all candidate analytes. The analytical performances of three extraction procedures and five combination of derivatization parameters were compared in order to probe the conditions for speeding up the sample preparation step. Limits of detection (LOD) were evaluated in both EI-MS and ECNI-MS (electron capture negative ionization mass spectrometry) modes, indicating better sensitivity for most of the analytes using the latter ionization technique. The use of short columns and high carrier gas velocity in fast GC/MS produced efficient separation of the analytes in less than 4 min, resulting in a drastic reduction of the analysis time, while a resolution comparable to that obtained from classic GC conditions is maintained. Fast quadrupole MS electronics allows high scan rates and effective data acquisition both in scan and selected ion monitoring modes.

Diuretics↗
PubMed2004

Determination of certain drugs in binary mixtures formulations by second derivative ratio spectrophotometry and LC.

Spectrophotometric and high-performance liquid chromatographic (HPLC) methods are developed for simultaneous determination of three binary mixtures with overlapping spectra. The spectrophotometric method is based on the use of second derivative of the ratio spectra (2DD) for resolution of three binary mixtures of indapamide with captopril (mixture 1), cinnarizine with heptaminol acefylline (mixture 2) and amoxycillin trihydrate with flucloxacillin sodium (mixture 3). The HPLC method depends on the separation of components of binary mixtures using ODS column with mobile phase consisting of acetonitrile and 5 mM aqueous heptane sulphonic acid sodium salt in ratios of (60:40, v/v, pH 5.5) for mixture 1, (50:50, v/v, pH 3.0) for mixture 2 and (35:65, v/v, pH 4.2) for mixture 3. The proposed methods are accurate, non-destructive and successfully applied for the determination of the three binary combinations in synthetic mixtures and commercial pharmaceutical products.

Chemistry, Pharmaceutical↗
PubMed1989

The relevance of plasma lipid changes with cardiovascular drug therapy.

Evidence is reviewed that thiazide diuretics increase plasma levels of triglycerides and LDL-cholesterol, and that most beta-blockers increase triglycerides and depress HDL-cholesterol. By contrast, indapamide, pindolol, and calcium channel blockers have little effect, and alpha 1-blockers and alpha 2-stimulants may improve the HDL- to LDL-cholesterol ratio.

Cardiovascular Agents↗
PubMed2005

[Discharge prescription for ischemic stroke patients].

Stroke is a major public health issue: it affects 120 000 people in France each year. The yearly recurrence rate is thought to reach 8 percent. Secondary prevention of stroke is thus crucial and focuses on controlling vascular risk factors most often associated with antiplatelet agents. Therapeutic objectives are set depending on the individual's global cardiovascular risk. The PROGRESS study has shown the relevance of systematic blood pressure lowering using an angiotensin-converting-enzyme inhibitor (perindopril) in combination with a diuretic (indapamide) in secondary prevention of stroke, including in normotensive patients. If possible, blood pressure should be below 130/85 mmHg. Statins are indicated in stroke patients with hypercholesterolemia, coronary heart disease, diabetes mellitus or carotid stenosis, the target LDL-cholesterol level being below 1 g/L (2.58 mmol/L). There is a wide consensus on treating patients with symptomatic carotid stenoses > or = 70 percent by thrombo-endarterectomy and stroke associated with atrial fibrillation by anticoagulants. Management should be global and include changes in dietary behavior, tobacco and/or alcohol withdrawal, and regular exercising. Patient-specific therapeutic education should be offered in order to improve compliance.

Atrial Fibrillation↗
PubMed2000

Efficacy and safety of valsartan compared with enalapril at different altitudes.

OBJECTIVE: To compare the safety, tolerability, and antihypertensive efficacy of valsartan with enalapril at different altitudes. METHOD: A total of 142 adult Colombian outpatients with mild to moderate essential hypertension were recruited in 3 cities at different altitudes (Bogotá at 2600 m, Medellin at 1538 m and Barranquilla at 100 m) and randomized in an open label fashion to receive either valsartan 80 mg once daily or enalapril 20 mg once daily for 8 weeks. Those patients not responding at 4 weeks received additional 1.25 mg indapamide daily during the remaining trial period. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to 4 weeks. Secondary efficacy variables included the change in mean sitting systolic blood pressure (SSBP). The primary criterion for tolerability was the incidence of adverse experiences. RESULTS: Both valsartan and enalapril reduced mean SDBP and SSBP with similar efficacy, independent of altitude. Adverse events irrespective of relationship to trial drug were reported by 12 patients (18.8%) on valsartan and by 15 (23.4%) patients on enalapril. Enalapril was associated with a significantly (P<0.05) higher rate of dry cough and more cases of headache than valsartan. CONCLUSIONS: Valsartan 80 mg once daily is as effective as enalapril 20 mg once daily in reducing blood pressure, with tolerability profile at least as good as enalapril's.

Adult↗
PubMed1999

Effect of hypertension and its treatment on lipid, lipoprotein(a), fibrinogen, and bilirubin levels in patients referred for dyslipidemia.

We measured the serum lipid profile, together with plasma fibrinogen and serum lipoprotein(a) (Lp[a]), glucose, bilirubin, and albumin levels in 491 patients (310 men) who were referred for the management of primary dyslipidemia. All these variables have been shown to predict vascular events. The patients were not taking lipid-lowering drugs; hypertension was present in 156 (31.7%) of them. Of the hypertensive patients, 52 (33%) were not receiving any treatment to control their blood pressure. This omission was not due to a lower prevalence of established vascular disease. The treated hypertensives were divided into three groups according to their treatment: 62 were taking lipid-hostile antihypertensives (beta-blockers, thiazides), 37 were taking lipid-neutral antihypertensives (angiotensin converting enzyme inhibitors, Ca-channel blockers, angiotensin II receptor blockers, indapamide sustained release), and five were taking lipid-friendly antihypertensives (doxazosin). Lipid-hostile antihypertensive drugs were associated with a significantly higher fibrinogen concentration when compared with untreated hypertensives or those taking lipid-neutral/lipid-friendly drugs (median values: 383, 353, and 336 mg/dL, respectively; P < .01). Lipid-neutral/lipid-friendly antihypertensive drugs were associated with lower Lp(a) levels when compared with untreated hypertensives (median values: 22 and 45 mg/dL, respectively; P < .05). The serum bilirubin level was significantly lower in the untreated hypertensives when compared with normotensives or the treated hypertensives. There were no significant differences in lipids, glucose, or albumin among the groups of hypertensives or normotensives. The influence of antihypertensive drugs on additional cardiovascular risk factors should be considered when selecting medication to reduce blood pressure.

Adult↗
PubMed1997

Inhibiting effects of antioxidants on drug-induced phototoxicity in cell cultures. Investigations with sulphonamide-derived oral antidiabetics and diuretics.

The sulphonamide-derived oral antidiabetics chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide, and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide were investigated for phototoxicity in a cell culture model. Cell death dependent on ultraviolet A (UVA) radiation fluence and test substance concentration was observed in the presence of the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at concentrations of 0.05 mM and above; bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at concentrations of 0.25 mM or more; the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at concentrations of 0.5 mM. To evaluate the effects of antioxidants, ascorbic acid, alpha-tocopherol, beta-carotene or ubiquinone was added to the tissue culture flasks before irradiation. The phototoxic inhibition of the colony-forming ability was largely reduced by the addition of ascorbic acid and alpha-tocopherole, indicating the involvement of reactive oxygen species in the phototoxic process.

Antioxidants↗
PubMed2003

[Secondary prevention after ischemic stroke].

This paper reviews secondary prevention of stroke by the therapy of vascular risk factors, anticoagulation, surgical and endovascular procedures. Two recently published studies, the PROtection aGainst REcurrent Stroke Study (PROGRESS) and the Heart Protection Study (HPS) demonstrated for the first time the efficacy of antihypertensive and lipid lowering by statins in stroke secondary prevention. PROGRESS has shown that the combination of perindoprile and indapamide reduced the occurrence of ischemic and hemorrhagic strokes in hyper- and normotensive patients by 40%, whereas HPS demonstrated a 20% reduction of ischemic strokes in cases with normal or elevated serum cholesterol. Symptomatic carotid stenoses with a distal degree of > or = 70% should undergo endarterectomy; in the presence of a distal degree of stenosis of 50-69% an individual treatment decision is performed; carotid surgery is not indicated in < 50% stenoses. Patients with a cardiac source of embolism (except those with cardiac myxoma or bacterial endocarditis) should be anticoagulated with a target INR of 2.5 (range 2-3). Patients who have no indication for vascular surgery or anticoagulation will be treated with platelet inhibitors. Aspirin 100 mg/d or the combination aspirin-dipyridamole are the treatment of choice. If cerebral ischemia reoccurs with aspirin or in case of aspirin intolerance clopidogrel will be administered. Patients with cerebral ischemia occurring while they are treated with clopidogrel may receive an oral anticoagulation with a target INR of 2.0 (range 1.5-2.5).

Administration, Oral↗
PubMed1999

Histamine H1-receptor-mediated modulation of the delayed rectifier K+ current in guinea-pig atrial cells: opposite effects on IKs and IKr.

1. Histamine receptor-mediated modulation of the rapid and slow components of the delayed rectifier K+ current (IK) was investigated in enzymatically-dissociated atrial cells of guinea-pigs using the whole cell configuration of the patch clamp technique. 2. Histamine at a concentration of 10 microM enhanced IK recorded during strong depolarization to potentials ranging from +20 to +40 mV and inhibited IK recorded during mild depolarization to potentials ranging from -20 to -10 mV. The increase of IK was more prominent with longer depolarizing pulses, whereas the inhibition of IK was more marked with shorter depolarizing pulses, suggesting that histamine enhances IKs (the slow component of IK) and inhibits IKr (the rapid component of IK). 3. The histamine-induced enhancement of IKs and inhibition of IKr were abolished by 3 microM chlorpheniramine but not by 10 microM cimetidine, suggesting that these opposite effects of histamine on IKr and IKs are mediated by H1-receptors. 4. In the presence of 5 microM E-4031, an IKr blocker, histamine hardly affected IK during mild depolarization although it enhanced IK during strong depolarization in a concentration-dependent manner. Histamine increased IKs with EC50 value of 0.7 microM. In the presence of 300 microM indapamide, an IKs blocker, histamine hardly affected IKs but inhibited IKr in a concentration-dependent manner. Histamine decreased IKr with IC50 value of 0.3 microM. 5. Pretreatment with 100 nM calphostin C or 30 nM staurosporine, protein kinase C inhibitors, abolished the histamine-induced enhancement of IKs, but failed to affect the histamine-induced inhibition of IKr. 6. We conclude that in guinea-pig atrial cells H1-receptor stimulation enhances IKs and inhibits IKr through different intracellular mechanisms.

Animals↗
PubMed2005

Managing hypertension: a question of STRATHE.

Current international guidelines recommend the use of therapeutic strategies with proven efficacy in the management of hypertension to achieve a target blood pressure of < 140/90 mmHg. After lifestyle intervention, they endorse three different management strategies: (i) first-line use of a low-dose combination of two agents from different antihypertensive classes, with the option of doubling the dose of the combination; (ii) use of a sequential monotherapy strategy, initiating with one antihypertensive to be replaced by another one from a different class, if necessary; and (iii) a stepped care strategy, initiating with one antihypertensive, and increasing the dose or adding another agent from a different class, if necessary. The objective of the STRAtegies of Treatment in Hypertension: Evaluation (STRATHE) study was to compare the efficacy and tolerability of these three treatment strategies in patients with uncomplicated essential hypertension (n = 533). In all, 62% of the patients in the low-dose combination group were normalised (< 140/90 mmHg), compared with 49% of the sequential monotherapy group (P = 0.01) and 47% of the stepped-care group (P = 0.005). The percentage of patients achieving normalisation without experiencing drug-related adverse events was also significantly higher in the low-dose combination group (56%) than in the sequential monotherapy (42%, P = 0.001) and stepped-care groups (42%, P = 0.004), consistent with the observation that the reduced dosage of the antihypertensive agents in such preparations translates into improved acceptability. The results of STRATHE provide further support for an antihypertensive management strategy involving the low-dose combination of perindopril (2 mg) and indapamide (0.625 mg).

Antihypertensive Agents↗
PubMed2005

Targeting endothelial dysfunction in hypertensive subjects.

The endothelium is a favourite early target of cardiovascular risk factors and cardiovascular diseases like hypertension. This key role of the endothelium results from its capacity to respond to numerous autocrine and paracrine stimuli and to mechanical factors like shear stress but also from the pathophysiological consequences of endothelial dysfunction on vasomotor tone, arterial stiffness, arterial remodelling, and inflammation, all of which are factors that play a critical role in atherosclerosis and target-organ damage. In hypertension, endothelial dysfunction has been shown at the level of both resistance and conduit arteries and mainly results from an increase in nitric oxide (NO) degradation by interaction between NO and superoxide anions, while in experimental models of hypertension a decrease in NO production can also be observed. The fact that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with hypertension stresses the importance of the clinical evaluation of endothelial function and of the evaluation of the effects of the different antihypertensive drug classes on this parameter. In this context, many studies have demonstrated that angiotensin-converting enzyme inhibitors, the perindopril-indapamide combination, and angiotensin II type I receptor (AT1) blockers improve endothelium-dependent vasodilatation partly independently of arterial pressure. Both their antioxidant effects and the stimulation of the release of NO are involved in their beneficial effects. For calcium antagonists, only the recent drugs have been shown to improve endothelial function with a simultaneous improvement in several markers of oxidative stress. Finally, beta-blockers classically do not affect endothelial function. Only nebivolol, a beta-blocker with NO donor properties, has been shown to improve endothelial function, but this effect results from the increase in NO and not from the beta-blocking properties of the drug.

Angiotensin-Converting Enzyme Inhibitors↗