Circulating adhesion molecules may have a prognostic significance as markers of endothelial damage. Drugs which inhibit the renin-angiotensin system may be effective in reducing circulating or tissue adhesion molecules, albeit data available are scarce. The aim of the study was to investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor, enalapril and a highly selective angiotensin receptor blocker, candesartan cilexetil, on circulating adhesion molecules in a large sample of patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was comparative, multicenter, randomized and double blind, with two parallel groups.
NIDDM patients with a diagnosis of mild (grade 1) essential hypertension were included in the study, at the end of a 2-week placebo run-in period. The primary end-point of the study was to evaluate changes of intercellular adhesion molecule-1 (ICAM-1) plasma levels during treatment. The secondary end-points were: changes in vascular cells adhesion molecule-1 (VCAM-1), von Willebrand factor (vWF), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) circulating levels and of urinary albumin excretion rate (AER) as well; 129 patients were randomized: 66 in the candesartan group and 63 in the enalapril group, 118 of them completed the scheduled 24-week treatment period.
Candesartan and enalapril equally reduced circulating level of ICAM-1 and exerted comparable effects on changes of other adhesion molecules and coagulation factors. A similar blood pressure-lowering effect was observed with the two drugs (candesartan: from 148/90 +/- 11/8 to 132/82 +/- 12/7 mmHg, P < 0.01, enalapril: from 148/91 +/- 12/8 to 131/85 +/- 14/6 mmHg, P < 0.01). Candesartan was more effective than enalapril in the reduction of albuminuria (P < 0.05 between treatments), although urinary protein excretion can be considered normal in the majority of patients. The two drugs were comparable in terms of adverse events reported.
Candesartan and enalapril showed similar effects on blood pressure and on circulating adhesion molecules. In this study urinary protein excretion was reduced more by candesartan.
"Enalapril is a dose-dependent antihypertensive drug, with its maximum effect occurring 6–8 hours after administration and a total duration of effect of 24–36 hours.40 Enalapril has been shown to be an effective antihypertensive agent, with positive effects on cardiovascular risk factors, prevention of decline in renal function and other organ damage,41–44 like progression of intima media thickness in the carotid artery, an independent risk factor for cardiovascular and cerebrovascular disease.43 The cardiovascular protection associated with enalapril may be caused by potentiation of the effects of bradykinin.45 "
[Show abstract][Hide abstract] ABSTRACT: Hypertension is one of the most important and widespread risk factors for the development of cardiovascular disease. Once, combination therapy was traditionally reserved as a third-line or fourth-line approach in the management of hypertension. However, several major intervention trials in high-risk patient populations have shown that an average of 2-4 antihypertensive agents are required to achieve effective blood pressure control. Combination treatment should be considered as a first choice in patients at high cardiovascular risk and in individuals for whom blood pressure is markedly above the hypertension threshold (eg, more than 20 mmHg systolic or 10 mmHg diastolic), or when milder degrees of blood pressure elevation are associated with multiple risk factors, subclinical organ damage, diabetes, renal failure, or associated cardiovascular disease. A number of clinical trials have demonstrated that a fixed combination of lercanidipine and enalapril has better efficacy and tolerability than monotherapy with either agents. The fixed-dose formulation of lercanidipine-enalapril was well tolerated in all clinical trials, with an adverse event rate similar to that of the component drugs as monotherapy. The advantages of combination therapy include improved adherence to therapy and minimization of blood pressure variability. In addition, combining two antihypertensive agents with different mechanisms of action may provide greater protection against major cardiovascular events and the development of end-organ damage.
"Candesartan improves endothelial function as evidenced by significantly increasing flow-mediated dilation in patients with hypertension, stable CAD, and endothelial dysfunction.49 Candesartan significantly improves the percent flow-mediated dilator response to hyperemia (P = 0.019); significantly decreases plasma levels of plasminogen activator inhibitor type-1 (PAI-1) antigen (P < 0.001) as well as monocyte chemoattractant protein-1 (P = 0.004),50 and significantly reduces circulating levels of ICAM-1 and VCAM-1 (P < 0.05).51 Candesartan has also been shown to slow the progression of carotid remodeling in patients with hypertension and type 2 diabetes.52 "
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular (CV) disease is a major factor in mortality rates around the world and contributes to more than one-third of deaths in the US. The underlying cause of CV disease is atherosclerosis, a chronic inflammatory process that is clinically manifested as coronary artery disease, carotid artery disease, or peripheral artery disease. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Consequently, developing a treatment regimen that can slow or even reverse the atherosclerotic process is imperative. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with CV risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. Since the renin-angiotensin-aldosterone system (RAAS) plays a key role in vascular inflammatory responses, hypertension treatment with RAAS-blocking agents (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II receptor blockers [ARBs]) may slow inflammatory processes and disease progression. Reduced nitric oxide (NO) bioavailability has an important role in the process of endothelial dysfunction and hypertension. Therefore, agents that increase NO and decrease oxidative stress, such as ARBs and ACEIs, may interfere with atherosclerosis. Studies show that angiotensin II type 1 receptor antagonism with an ARB improves endothelial function and reduces atherogenesis. In patients with hypertension, the ARB olmesartan medoxomil provides effective blood pressure lowering, with inflammatory marker studies demonstrating significant RAAS suppression. Several prospective, randomized studies show vascular benefits with olmesartan medoxomil: reduced progression of coronary atherosclerosis in patients with stable angina pectoris (OLIVUS); decreased vascular inflammatory markers in patients with hypertension and micro- (pre-clinical) inflammation (EUTOPIA); improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis (MORE); and resistance vessel remodeling in patients with stage 1 hypertension (VIOS). Although CV outcomes were not assessed in these studies, the observed benefits in surrogate endpoints of disease suggest that RAAS suppression with olmesartan medoxomil may potentially have beneficial effects on CV outcomes in these patient populations.
Vascular Health and Risk Management 06/2011; 7(1):405-16. DOI:10.2147/VHRM.S20737
"Moreover, the treatment with ACE inhibitors reversed the increase in the production of superoxide anions and the activation of NF-kB system, as well as the elevated expression of pro-inflammatory cytokines, in aortas of rat with reduced NO synthesis  and in a rabbit model of atherosclerosis . Also, a reduction in the circulating levels of intercellular adhesion molecule-1 (ICAM-1) has been observed in hypertensive patients  and in human aortic endothelial cells  after the treatment with an ACE inhibitor. "
[Show abstract][Hide abstract] ABSTRACT: Captopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the treatment of arterial hypertension and cardiovascular diseases. Our objective was to study whether captopril is able to attenuate the cardiac inflammatory process associated with arterial hypertension.
Left ventricle mRNA expression and plasma levels of pro-inflammatory (interleukin-1beta (IL-1beta) and IL-6) and anti-inflammatory (IL-10) cytokines, were measured in spontaneously hypertensive rats (SHR) and their control normotensive, Wistar-Kyoto (WKY) rats, with or without a 12-week treatment with captopril (80 mg/Kg/day; n = six animals per group). To understand the mechanisms involved in the effect of captopril, mRNA expression of ACE, angiotensin II type I receptor (AT1R) and p22phox (a subunit of NADPH oxidase), as well as NF-kappaB activation and expression, were measured in the left ventricle of these animals.
In SHR, the observed increases in blood pressures, heart rate, left ventricle relative weight, plasma levels and cardiac mRNA expression of IL-1beta and IL-6, as well as the reductions in the plasma levels and in the cardiac mRNA expression of IL-10, were reversed after the treatment with captopril. Moreover, the mRNA expressions of ACE, AT1R and p22phox, which were enhanced in the left ventricle of SHR, were reduced to normal values after captopril treatment. Finally, SHR presented an elevated cardiac mRNA expression and activation of the transcription nuclear factor, NF-kappaB, accompanied by a reduced expression of its inhibitor, IkappaB; captopril administration corrected the observed changes in all these parameters.
These findings show that captopril decreases the inflammation process in the left ventricle of hypertensive rats and suggest that NF-kappaB-driven inflammatory reactivity might be responsible for this effect through an inactivation of NF-kappaB-dependent pro-inflammatory factors.
Journal of Inflammation 05/2010; 7(1):21. DOI:10.1186/1476-9255-7-21 · 2.02 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.