Effects Of Different Antihypertensive Treatments Research Articles

Antihypertensive treatment of end-stage renal disease patients on hemodialysis does not alter circulating ACE and ACE2 activity and angiotensin peptides

Cardiovascular diseases (CVD) are the main causes of death in hemodialysis patients, representing a public health challenge. We investigated the effect of different antihypertensive treatments on circulating levels of renin-angiotensin system (RAS) components in end-stage renal disease (ESRD) patients on hemodialysis. ESRD patients were grouped following the prescribed antihypertensive drugs: ß-blocker, ß-blocker+ACEi and ß-blocker+AT1R blocker. ESDR patients under no antihypertensive drug treatment were used as controls. Blood samples were collected before hemodialysis sessions. Enzymatic activities of the angiotensin-converting enzymes ACE and ACE2 were measured through fluorescence assays and plasma concentrations of the peptides Angiotensin II (Ang II) and Angiotensin-(1–7) [Ang-(1–7)] were quantified using mass spectrometry (LC-MS/MS). ACE activity was decreased only in the ß-blocker+ACEi group compared to the ß-blocker+AT1R, while ACE2 activity did not change according to the antihypertensive treatment. Both Ang II and Ang-(1–7) levels also did not change according to the antihypertensive treatment. We concluded that the treatment of ESRD patients on hemodialysis with different antihypertensive drugs do not alter the circulating levels of RAS components.

Blood Pressure Variability as a Risk Factor for Cardiovascular Disease: Which Antihypertensive Agents Are More Effective?

Blood pressure oscillations during different time scales, known as blood pressure variability (BPV), have become a focus of growing scientific interest. BPV can be measured at long-term (seasonal variability or visit-to-visit), at mid-term (differences in consecutive days or weeks) or at short-term (day-night differences or changes induced by other daily activities and conditions). An increased BPV, either at long, mid or short-term is associated with a poor cardiovascular prognosis independently of the amount of blood pressure elevation. There is scarce evidence on the effect of different antihypertensive treatments on BPV, but some observational and interventional studies suggest that calcium channel blockers in general, and particularly amlodipine, either in monotherapy or combined with renin-angiotensin system blockers, can reduce BPV more efficiently than other antihypertensive drugs or combinations. Nevertheless, there are several aspects of the relationship between BPV, antihypertensive treatment, and clinical outcomes that are still unknown, and more work should be performed before considering BPV as a therapeutical target in clinical practice.

Long-Term Antihypertensive Treatment Fails to Improve E/e′ Despite Regression of Left Ventricular Mass

Antihypertensive treatment can improve tissue Doppler indices of left ventricular diastolic function in the short term, but little is known about the longer-term effect of different antihypertensive treatments on progression of left ventricular diastolic function and left ventricular hypertrophy. We hypothesized that long-term treatment of hypertension will lead to improvements in left ventricular hypertrophy and diastolic function. We collected detailed cardiovascular phenotypic data on 1006 participants from a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial. Patients randomized to either an amlodipine±perindopril-based or an atenolol±bendroflumethiazide-based regimen underwent conventional and tissue Doppler echocardiography at time of control of blood pressure after randomization (≈1.5 years; phase 1) and after a further 2 years of antihypertensive treatment (phase 2). There were no prerandomization data. Five hundred thirty-six patients had complete data collection at both phases. Left ventricular mass index regressed from phase 1 to 2 with no significant difference between treatment groups (amlodipine: 119.5–116.8; atenolol: 122.9–117.5; P <0.001 for both). Conversely, tissue Doppler diastolic indices did not change in the amlodipine±perindopril-based regimen (E/e′, 7.5–7.6 cm/s; P =not significant), but deteriorated in the atenolol±bendroflumethiazide-based regimen (E/e′, 8.0–8.5 cm/s; P <0.01). Despite regression of left ventricular hypertrophy, there was no associated improvement in diastolic function. In fact, long-term treatment with atenolol±bendroflumethiazide resulted in a progressive deterioration in E/e′. This may be a factor contributing to the previously described worse clinical outcome in patients treated with atenolol±bendroflumethiazide compared with amlodipine±perindopril.

Effect of different antihypertensive treatments on Ras, MAPK and Akt activation in hypertension and diabetes

Ras GTPases function as transducers of extracellular signals regulating many cell functions, and they appear to be involved in the development of hypertension. In the present study, we have investigated whether antihypertensive treatment with ARBs (angiotensin II receptor blockers), ACEi (angiotensin-converting enzyme inhibitors) and diuretics induce changes in Ras activation and in some of its effectors [ERK (extracellular-signal-regulated kinase) and Akt] in lymphocytes from patients with hypertension without or with diabetes. ACEi treatment transiently reduced Ras activation in the first month of treatment, but diuretics induced a sustained increase in Ras activation throughout the 3 months of the study. In patients with hypertension and diabetes, ARB, ACEi and diuretic treatment increased Ras activation only during the first week. ACEi treatment increased phospho-ERK expression during the first week and also in the last 2 months of the study; however, diuretic treatment reduced phospho-ERK expression during the last 2 months of the study. In patients with hypertension and diabetes, antihypertensive treatments did not induce changes in phospho-ERK expression in lymphocytes. ACEi treatment reduced phospho-Akt expression in patients with hypertension and diabetes only in the first month of treatment. In conclusion, these findings show that antihypertensive treatments with ACEi, and diuretics to a lesser extent, modify Ras activation and some of its signalling pathways, although in different directions, whereas ARBs do not appear to have any influence on Ras signalling pathways.

Quantitative Ultrasonographic Evaluation of the Carotid Arteries in Hypertension

Current treatment goals for hypertension include the prevention of end-organ injuries. Hypertension is certainly among the major contributors to atherogenesis, and many antihypertensive drugs seem to have wall-protecting properties. It is critical to identify, test, and implement non-invasive methods for the screening of the population in order to detect early wall abnormalities and to monitor the long-term effects of different antihypertensive treatments. Among these methods, B-mode ultrasound examination of carotid arteries has shown great potential in evaluating treatments that may prevent hypertension-related wall injuries.

Effects of different antihypertensive treatments on morphologic progression of diabetic nephropathy in uninephrectomized dogs

We previously reported the renal hemodynamic effects of different antihypertensive regimens in uninephrectomized, alloxan-induced, diabetic (DM) beagle dogs following one year of treatment. Dogs were prospectively randomized to one of five groups (N = 26): nondiabetic controls, Group I; dogs with DM on no antihypertensive drugs, Group II; dogs on a converting enzyme inhibitor, lisinopril (L), Group III; dogs on a calcium antagonist, TA3090 (diltiazem-like), Group IV; and dogs on a combination of each drug, in reduced doses, Group V. The current paper extends our previous studies by describing the morphologic changes that occurred within each group of dogs studied. More than 100 glomeruli from the renal cortex of each dog were evaluated for increases in mesangial volume fraction (Vv), glomerulosclerosis (GS) and ateriolar hyalinosis. The interstitium was also evaluated for associated changes. Increases in Vv were attenuated in all treated groups (0.28 +/- 0.04, DM alone versus 0.16 +/- 0.05 L; 0.21 +/- 0.07, TA-3090; 0.19 +/- 0.06 micron 2/micron 2, L+TA 3090; P < 0.05) compared to untreated DM. An attenuated increase in Vv also correlated with a blunted rise in proteinuria in Groups III (r = 0.79) and V (r = 0.81) but not Group IV (r = 0.29). Development of focal GS was blunted in all treated groups; however, global GS was fourfold greater in Group IV compared to untreated DM. The degree of interstitial fibrosis also correlated with the degree of global GS. These data support the concept that both a converting enzyme inhibitor and heart rate lowering calcium antagonist attenuate morphologic progression of diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative Effects of Different Antihypertensive Treatments on Progression of Diabetic Renal Disease

Given the same level of arterial pressure control, studies in diabetic animal models have demonstrated certain classes of antihypertensive medication to confer better overall preservation of renal histologic features and function as well as reduced albuminuria when compared with other agents. The present study was designed to assess whether any differences exist among antihypertensive agents with regard to progression of diabetic renal disease and albuminuria in human subjects. The study was a randomized, prospective, parallel group design that evaluated the effects of a converting enzyme inhibitor (lisinopril; group 1), a calcium antagonist (diltiazem hydrochloride; group 2), and a combination of a loop diuretic and a beta-blocker (furosemide and atenolol; group 3) in 30 subjects. All subjects received a low-salt, low-protein diet. Metabolic (blood glucose, cholesterol profiles, and urine urea nitrogen and sodium levels) as well as renal hemodynamic (renal blood flow and glomerular filtration rate) profiles and arterial pressure measurements were performed at various intervals during an 18-month period. Both groups 1 and 2 had significantly slower rates of decline in glomerular filtration rate compared with group 3. No significant differences were observed in renal hemodynamics between groups 1 and 2 at 18 months. Group 3 had the worst metabolic, lipid, and side-effect profile of any group. Reductions in albuminuria were not different between groups 1 and 2, but both were significantly reduced compared with group 3. Given a similar level of arterial pressure control, both lisinopril and diltiazem slow progression of diabetic renal disease and reduce albuminuria to a greater extent than does the combination of a loop diuretic and beta-adrenoreceptor antagonist. These drugs were also better tolerated and produced no adverse metabolic effects.

Comparative effects of different antihypertensive treatments on progression of diabetic renal disease

Comparative effects of different antihypertensive treatments on progression of diabetic renal disease