Decrease In Plasma Renin Activity Research Articles

High Fructose-Induced Hypertension and Renal Damage Are Exaggerated in Dahl Salt-Sensitive Rats via Renal Renin-Angiotensin System Activation.

BackgroundHigh‐fructose diet (HFr) induces hypertension and renal damage. However, it has been unknown whether the HFr‐induced hypertension and renal damage are exaggerated in subjects with salt sensitivity. We tested impacts of HFr in Dahl salt‐sensitive (DS) and salt‐resistant (DR) rats.Methods and ResultsMale DS and DR rats were fed control diet or HFr (60% fructose) with normal‐salt content. After 12 weeks, plasma and urinary parameters, renal histological characteristics, and renal expression of renin‐angiotensin system components were examined. Furthermore, effects of renin‐angiotensin system inhibitors were also examined in DS rats fed the HFr. HFr elevated blood pressure in DS rats but not in DR rats. HFr increased urinary albumin and liver type fatty acid binding protein excretions in both rats, but the excretions were exaggerated in DS rats. HFr increased plasma lipids and uric acid in both rats, whereas HFr increased creatinine clearance in DS rats but not DR rats. Although HFr decreased plasma renin activity in DS rats, HFr‐induced glomerular injury, afferent arteriolar thickening, and renal interstitial fibrosis were exaggerated in DS rats. HFr increased renal expression of angiotensinogen, renin, (pro)renin receptor, angiotensin‐converting enzyme, and angiotensin II type 1 receptor in DS rat, whereas HFr increased only angiotensin‐converting enzyme expression and decreased renin and angiotensin II type 1 receptor expressions in DR rats. Enalapril and candesartan attenuated the HFr‐induced hypertension, albuminuria, glomerular hyperfiltration, and renal damage in DS rats.ConclusionHFr‐induced hypertension and renal damage are exaggerated in DS rats via renal renin‐angiotensin system activation, which can be controlled by renin‐angiotensin system inhibitors.

Conversion of Propranolol to Carvedilol Improves Renal Perfusion and Outcome in Patients With Cirrhosis and Ascites.

In recent years, concerns have been raised on the potential adverse effects of nonselective beta-blockers, and particularly carvedilol, on renal perfusion and survival in decompensated cirrhosis with ascites. We investigated the long-term impact of converting propranolol to carvedilol on systemic hemodynamics and renal function, and on the outcome of patients with stable cirrhosis and grade II/III nonrefractory ascites. Ninety-six patients treated with propranolol for esophageal varices' bleeding prophylaxis were prospectively evaluated. These patients were randomized in a 2:1 ratio to switch to carvedilol at 12.5 mg/d (CARVE group; n=64) or continue propranolol (PROPRA group; n=32). Systemic vascular resistance, vasoactive factors, glomerular filtration rate, and renal blood flow were evaluated at baseline before switching to carvedilol and after 6 and 12 months. Further decompensation and survival were evaluated at 2 years. During a 12-month follow-up, carvedilol induced an ongoing improvement of systemic vascular resistance (1372±34 vs. 1254±33 dynes/c/cm5; P=0.02) along with significant decreases in plasma renin activity (4.05±0.66 vs. 6.57±0.98 ng/mL/h; P=0.01) and serum noradrenaline (76.7±8.2 vs. 101.9±10.5 pg/mL; P=0.03) and significant improvement of glomerular filtration rate (87.3±2.7 vs. 78.7±2.3 mL/min; P=0.03) and renal blood flow (703±17 vs. 631±12 mL/min; P=0.03); no significant effects were noted in the PROPRA group. The 2-year occurrence of further decompensation was significantly lower in the CARVE group than in the PROPRA group (10.5% vs. 35.9%; P=0.003); survival at 2 years was significantly higher in the CARVE group (86% vs. 64.1%; P=0.01, respectively). Carvedilol at the dose of 12.5 mg/d should be the nonselective beta-blocker treatment of choice in patients with cirrhosis and nonrefractory ascites, as it improves renal perfusion and outcome.

Labetalol Infusion Attenuates Paradoxical Hypertension and Decreases Plasma Renin Activity After Repair of Coarctation of the Aorta in Children

Paradoxical hypertension after repair of coarctation of the aorta in children is associated with the release of catecholamines and activation of the renin-angiotensin system. The objective of the present study was to describe the effects of labetalol infusion on blood pressure, plasma catecholamine levels, and plasma renin activity in a series of children undergoing repair of coarctation of the aorta. Prospective, observational cohort study. Tertiary children's hospital with university affiliation. The study was comprised of 15 consecutive children older than 1 year undergoing repair of coarctation of the aorta. Intravenous infusion of labetalol, up to 20 µg/kg/min, was administered when patients became hypertensive after release of the aortic cross-clamp. Supplementation with nitroprusside was allowed as needed. Blood pressure was maintained below baseline values throughout the labetalol infusion. Plasma norepinephrine increased from 160 ± 81 pg/mL (preoperative) to 657 ± 268 pg/mL (6 h after release of aortic cross-clamp). Plasma renin activity decreased from 16.6 ± 9.7 ng/kg/h (at cross-clamp release) to 2.2 ± 2.2 ng/kg/h (6 h after cross-clamp release). Nitroprusside was added for 12 patients, at a highest mean dose of 2.4 ± 2.5 μg/kg/min. Labetalol inhibited activation of the renin-angiotensin system and helped control paradoxical hypertension after coarctation repair in children.

Pool walking may improve renal function by suppressing the renin-angiotensin-aldosterone system in healthy pregnant women

This study aimed to examine the effect of pool walking on renal function in pregnant women. Fifteen pregnant women (mean gestational age, 37.8 weeks) walked in a pool (depth 1.3 m) for 1 h. A few days later, they walked on a street for 1 h. Within each activity, the starting and ending levels of plasma renin activity were measured. The total urine volume, creatinine clearance, and change in plasma renin activity levels between each activity were compared by Wilcoxon rank-sum test. The renin-angiotensin-aldosterone level was suppressed during pool walking: the mean starting and ending values of plasma renin activity and serum aldosterone were 6.8 vs. 5.5 ng/mL/h (p = 0.002) and 654 vs. 473 pg/mL (p = 0.01), respectively. The decreases in plasma renin activity and serum aldosterone levels were more evident in pool walking than in land walking (plasma renin activity, −1.27 vs. 0.81 ng/mL/h, p = 0.002; serum aldosterone, −180.9 vs. 3.1 ng/mL/h, p = 0.03), resulting in higher total urine volume (299 vs. 80 mL, p < 0.001) and creatinine clearance (161.4 vs. 123.4 mL/min, p = 0.03) in pool walking. Pool walking may improve renal function in pregnant women partly through the suppressed renin-angiotensin-aldosterone system.

Abstract 027: Changes in Renin Angiotensin System Monitored Across Time Following Bariatric Surgery

There is scarce information regarding the complete renin-angiotensin-aldosterone system (RAAS) and its changes after bariatric surgery (BS) in patients with morbid obesity (MO). Objective: to analyze changes (Δ) in RAAS components in MO after BS at several follow-up time points. Methods: Fifty-five MO patients (78% women, 40% hypertensives, age 43.4±8.9yr, BMI 42.4±5.3Kg/m 2 ) were evaluated prospectively before and 1,3,6 and 12 months(m) after BS, with assessment of anthropometrics, RAAS components and 24h-systolic BP (SBP). Results: at 12m body weight (-35.1±9.7 Kg) and waist circumference (-27±9.2 cm) decreased (p&lt;0.001). At 1,3 and 6m, there was a reduction in angiotensin-converting enzyme (ACE) and ACE-2 activity, as well as a decrease in plasma renin activity (PRA) and aldosterone from 3m on (Table). The decrease in 24h-SBP at 1m was 6.2 mmHg (3.6 to 8.8), p&lt;0.001. There were correlations (p&lt;0.05) between ΔPRA/Δ24h-SBP at 1m (r=-0.332), 3m (r=-0.330) and 12m (r=-0.322). ΔPRA and Δbody weight correlated only at 1m (r=-0.427). Δaldosterone and Δwaist circumference correlated at 12m (r=-0.372). ΔACE and Δ24h-SBP correlated at 6 and 12m (r=0.451 and r=0.635, respectively). Correlations between Δ24h-SBP and Δbody weight were statistically significant only at 6m (r=0,366; p=0,016). Conclusions: there are sequential changes in several components of the RASS after BS, with an increase in ACE and ACE2 activity as early as 1m after BS that lasts until 6m, and a decrease in PRA and plasma Aldosterone that initiates at 3m and remains 12m after BS. These changes correlate with the decrease of 24h-SBP. RAAS components, but not body weight, appear to correlate with changes in BP after BS.

Endocrine hypertension in an internal medicine department

Endocrine arterial hypertension (HT) is rare; its overall prevalence does not exceed 4% of hypertensive patients. Research interest in endocrine HT is due to the severity of some life-threatening, potentially curable and reversible forms of HT. We aimed to determine the clinical, paraclinical, etiological and therapeutic profile of secondary endocrine HT in patients treated in our department of internal medicine. Twenty-seven patients were diagnosed with endocrine HT; 11 males and 16 females, mean age 42 years old. HT duration ranged from one month to 24 years. 13 cases of neuroendocrine tumors were diagnosed: 11 pheochromocytoma and 2 para-ganglioma. Patients with neuroendocrine tumors had the classic triad of diaphoresis, headache and palpitation associated with cathecholamine/metanephrine excess. The tumor was localized by magnetic resonance or 123 I–MIBG imaging and the diagnosis was confirmed by pathological examination after surgery. We diagnosed 6 cases of Conn adenoma, 5 cortical carcinomas, 1 pulmonary cancer's adrenal metastasis, 1 adrenal hyperplasia and 1 hyperaldosteronism secondary to treatment with Ergoloid. The diagnosis was confirmed by hormone dosage evidencing elevated plasma aldosterone levels and decreased plasma renin activity in cases of Conn adenoma and adrenal hyperplasia, hyper-cortisolemia in cases of cortical adenoma, cortical carcinoma and pulmonary cancer's adrenal metastasis. The tumor was localized by CT scan and the diagnosis was confirmed by pathological examination after surgery. Blood pressure normalization was found among 16 patients after surgery. Endocrine HT has many etiologies possibly responsible for high morbidity and mortality, especially when not properly diagnosed or treated. The potentially curable nature of endocrine HT in more than two thirds of cases, demonstrates the importance of early diagnosis of every severe HT resistant to treatment or in the presence of suggestive clinical, biological or radiological signs.

ENDOCRINE HYPERTENSION (HYPERTENSION) IN A DEPARTMENT OF INTERNAL MEDICINE

Objective: The aim of our study was to determine the clinical, paraclinical, etiological and therapeutic profile of secondary HTA of endocrine origin in patients treated in internal medecine department at the University Hospital Sahloul in Tunisia. Design and method: This study investigated various clinicalpathological factors of 27 patients who were diagnosed with endocrine HTA in patients hospitalized in internal medecine department at the University Hospital Sahloul in Tunisia. Results: There were 11 male and 16 female patients. The mean age was 42 years. HTA's average duration of evolution ranged from one month to 24 years. There were 13 cases of neuroendocrine tumors: 11 cases of pheochromocytoma and 2 cases of paraganglioma. Patients with Neuroendocrine tumors had the classic triad of diaphoresis, headache and palpitation associated with cathecholamine/metanephrine excess. The tumor was localized by magnetic resonance imaging(MRI) or 123 I –MIBG imaging and the diagnosis was confirmed by pathological examination after surgery. We have found 6 cases of Conn adenoma, 5 cases of cortical carcinoma, one case of pulmonary cancer's adrenal metastasis, one case of adrenal hyperplasia and one case of hyperaldosteronism secondary to treatment with Ergoloid. The diagnosis was confirmed by hormone dosage which showed elevated plasma aldosterone levels and decreased plasma renin activity in cases of Conn adenoma and adrenal hyperplasia, hypercortisolemia in cases of cortical adenoma, cortical carcinoma and pulmonary cancer's adrenal metastasis. The tumor was localized by CT scann and the diagnosis was confirmed by pathological examination after surgery. Blood pressure normalization was found among16 patients after surgery. Conclusions: HTA of endocrine origin has many etiology witch could have high morbidity and mortality, especially when not properly diagnosed or treated. The potentially curable nature of HTA in more than two thirds of cases, demostrates the importance of early diagnosis of each severe HTA resistant to treatment or in the presence of suggestive clinical, biological or radiological signs.

Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial

Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT. A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels. There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly. In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival. Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.

Prenatal exposure to angiotensin II increases blood pressure and decreases salt sensitivity in rats

ABSTRACTRenin angiotensin aldosterone system (RAAS) plays an essential role in the homeostatic control of arterial blood pressure, perfusion of tissues, and control of extracellular fluid. Its components are highly expressed in the developing kidney, general vasculature, brain, and heart. A modified intrauterine environment alters mechanisms controlling blood pressure (BP) and can lead to hypertension in the adult offspring and developmentally programmed RAAS can be involved in this process. There are very little data about the effects of increased angiotensin II (Ang II) concentrations during pregnancy on in utero development of the fetus. In our study, we administered Ang II to pregnant female rats via osmotic mini-pumps and evaluated the postnatal development and BP control in the offspring. To estimate possible developmental changes in sensitivity to salt, we exposed the offspring to a diet with increased salt content and measured plasma aldosterone levels and plasma renin activity. Increased Ang II during pregnancy raised BP in the offspring; however, salt sensitivity was decreased in comparison to controls. Relative weight of the left ventricle was decreased in the offspring prenatally exposed to Ang II, while relative kidney weight was reduced only in female offspring. Prenatal treatment led to increased aldosterone levels and decreased plasma renin activity, suggesting a complex physiological response. Our results suggest that conditions leading to upregulation of RAAS during pregnancy can influence the cardiovascular system of the fetus and have a long-term impact on the offspring’s health.

Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension.

Renovascular hypertension (RVH) is a result of renal artery stenosis, which is commonly due to astherosclerosis. In this study, we aimed to clarify the central and peripheral effects of ghrelin on the renin-angiotensin system (RAS) in a rat model of RVH. RVH was induced in rats by partial subdiaphragmatic aortic constriction. Experiment A was designed to assess the central effect of ghrelin via the intracerebroventricular (ICV) injection of ghrelin (5 μg/kg) or losartan (0.01 mg/kg) in RVH rats. Experiment B was designed to assess the peripheral effect of ghrelin via the subcutaneous (SC) injection of ghrelin (150 μg/kg) or losartan (10 mg/kg) for 7 consecutive days. Mean arterial blood pressure (MAP), heart rate, plasma renin activity (PRA), and oxidative stress markers were measured in all rats. In addition, angiotensin II receptor type 1 (AT1R) concentration was measured in the hypothalamus of rats in Experiment B. RVH significantly increased brain AT1R, PRA, as well as the brain and plasma oxidative stress. Either SC or ICV ghrelin or losartan caused a significant decrease in MAP with no change in the heart rate. Central ghrelin or losartan caused a significant decrease in brain AT1R with significant alleviation of the brain oxidative stress. Central ghrelin caused a significant decrease in PRA, whereas central losartan caused a significant increase in PRA. SC ghrelin significantly decreased PRA and plasma oxidative stress, whereas SC losartan significantly increased PRA and decreased plasma oxidative stress. The hypotensive effect of ghrelin is mediated through the amelioration of oxidative stress, which is induced by RAS centrally and peripherally.

Hemodynamic responses to mental stress during salt loading.

The purpose was to examine whether prolonged moderate stress associated with a student exam would increase the blood pressure response to a salt load in young healthy normotensive individuals. Ten healthy young subjects were examined at two different occasions in random order (i) during preparation for a medical exam (prolonged stress) and (ii) outside the exam period (low stress). All subjects consumed a controlled diet for 3days with low- or high-salt content in randomized order. The subjective stress was measured by Spielberger's State-Trait Anxiety Inventory-Scale, SCL Symptom Checklist for stress and the Visual Analogue Scale. On each level of stress, 24-h ambulatory blood pressure and cardiac output (CO) were measured. Furthermore, plasma norepinephrine (NE), epinephrine (E) and plasma renin activity (PRA) were measured. Twenty-four-hour ABP, 24-h heart rate, CO as well as plasma levels of NE, E and PRA remained unchanged by changes in stress level. Day-night reduction in SAP was significantly larger during moderate stress and high-salt intake; however, no significant difference was observed during daytime and night-time. Individual increase in mental stress correlated significantly with an individual decrease in PRA (SCL-17, r=-0·80, P<0·05, STAIr=-0·64 P<0·05) during high-salt intake. Moderate stress over a period of time in young healthy normotensiveindividuals does not lead to changes in 24-h ABP. However, the augmented reduction in day-to-night systolic blood pressure during high-salt intake and moderate stress may indicate that stress affects blood pressure regulation.

Динамика показателей структурно-функционального состояния сердца, сосудов, почек и содержания в крови ренина и альдостерона при лечении блокаторами ренин-ангиотензин-альдостероновой системы больных гипертонической болезнью с сопутствующим хроническим пиел

SUMMARY. The dynamics of indicators of structural and functional state of the heart, blood vessels, kidneys and neurohumoral status in patients with essential hypertension (EH) 1 degree with concomitant chronic pyelonephritis (CRD) and chronic heart failure (CHF) II functional class (FC) with preserved left ventricular ejection fraction (LVEF) of the heart was studied. It is proved that the treatment of hypertensive patients with chronic renal failure 1 degree and CHF FC II by renin-angiotensin-aldosterone system (RAAS) blockers – angiotensin-converting enzyme (ACE) inhibitors spirapril a daily dose of 3 mg, candesartan in a daily dose of 16-24 mg, combination ACE inhibitors spirapril a daily dose of 3 mg and direct renin inhibitor aliskiren in a daily dose of 150 mg – leads to reliable comparable increases in distance of the 6-minute walk test, LVEF, endothelium-dependent vasodilation (EDVD), glomerular filtration rate (GFR) and reliable reducing the size of the left atrium, end-diastolic diameter (EDD) and end-systolic diameter (ESD), the mean pulmonary artery pressure (PASP), aldosterone and daily albuminuria. The efficacy of antihypertensive therapy in patients with EH 1 degree with chronic CKD and heart failure class II combination of ACE inhibitors spirapril and direct renin inhibitor aliskiren during 14 weeks exceeds the effects of monotherapy with ACE inhibitors and is accompanied by a significantly greater reduction in the EDD, myocardial mass index, plasma aldosterone blood significantly greater increases in GFR, EDVD and decreased plasma renin activity with an increase in the latter during treatment with ACE inhibitors. KEY WORDS: RAAS blockers, spirapril, hypertension, chronic pyelonephritis, chronic heart failure.

Randomized Controlled Trial Comparing the Efficacy of Terlipressin and Albumin with a Combination of Concurrent Dopamine, Furosemide, and Albumin in Hepatorenal Syndrome

Terlipressin with albumin is recommended in hepatorenal syndrome (HRS). Terlipressin is expensive and not licensed in many countries. Alternative therapy is necessary. We compared the efficacy of terlipressin and albumin with concurrent low-dose dopamine, furosemide, and albumin in HRS. In an open-label, randomized trial, forty consecutive patients each with HRS type I and HRS type II received either concurrent infusion of terlipressin 0.5mg for every 6hr and albumin 20g/day for 5 days (n=20) or a combination of dopamine 2μg/kg/min, furosemide 0.01mg/kg/hr, and albumin 20g/day (triple therapy), in one of two therapeutic arms. Twenty-four-hour urine output, urinary sodium, and plasma renin activity (PRA) were assessed before and after treatment. The two groups were comparable at baseline in both HRS-I and II. In HRS-I, 24hr urine output and urine sodium at the end of 5 days increased in both treatment groups (terlipressin, urine output 278±136 to 765±699ml/day, P<0.01; urine sodium 28±25.1 to 39±32.1meq/l, P=0.05. Triple therapy: urine output 219±134 to 706±595ml/day, P<0.01; urine sodium 25±18.3 to 41±27.5meq/l, P<0.01). PRA (ng/ml/hr) decreased from 28.1±9.76 to 24.2±9.5 (P=0.01) and from 29.5±15.8 to 27.3±17.1 (P=0.02) in the terlipressin and triple therapy groups, respectively. In HRS-II, similar significant improvement (P<0.01) was seen in 24hr urine output and urine sodium; decrease in PRA (P<0.05) was documented after treatment in both the arms. Post-treatment changes in parameters were comparable between the two arms, in both HRS-I and HRS-II cases. Concurrent triple therapy improved renal function in HRS and was less expensive than terlipressin (Registration: CTRI/2011/07/001860; www.ctri.nic.in).

Biochemical and histological impact of direct renin inhibition by aliskiren on myofibroblasts activation and differentiation in bleomycin induced pulmonary fibrosis in adult mice.

Aliskiren is a drug classified as a direct renin inhibitor. The renin-angiotensin system plays an important role in pulmonary fibrogeneses. This study aimed to investigate the impact of aliskiren on pulmonary fibrosis induced by bleomycin. Forty adult mice were divided into group I (control), group II (aliskiren 25mg/kg/day IP), group III (bleomycin 0.035U/g intraperitoneally twice weekly for 4 weeks) and group IV (aliskiren+bleomycin). Plasma renin activity (PRA), lung content of hydroxyproline and transforming growth factor-β1 (TGF-β1) were assayed. Lung paraffin sections were prepared for histological study and immunohistochemical detection of alpha smooth muscle actin (αSMA) as a marker for myofibroblasts activation and differentiation. Bleomycin induced a significant elevation of PRA with a significant increase in hydroxyproline and TGF-β1 in group III. Microscopically, pulmonary fibrosis was evident in the form of areas of collapsed alveoli, intense inflammatory cells infiltrations, excess accumulation of collagen, and excessively encountered αSMA positively immune-stained myofibroblasts, compared to a negative immune-reaction in groups I and II. In group IV, aliskiren resulted in a significant decrease in PRA, TGF-β1 and hydroxyproline, with an attenuation of pulmonary fibrosis and a decrease in αSMA positively immune-stained myofibroblasts. In conclusion, renin inhibition by aliskiren attenuated pulmonary fibrosis through decreasing TGF-β1 and myofibroblasts activation and differentiation.

Renin inhibitors in diabetes and hypertension: an update.

The coexistence of hypertension and diabetes increases the incidence of cardiovascular events and long-term morbidity and mortality. Blood pressure should be controlled with the most appropriate drugs as well as tight blood glucose control in patients with diabetes and hypertension. RAAS (Renin Angiotensin Aldosterone System) blockers have an important role in the treatment of these patients, in this sense, ACEi and ARB remained the major treatment option in hypertension guidelines. The most recent RAAS blocker to be approved by the FDA was aliskiren in 2007, a renin inhibitor. Studies showed that aliskiren is as effective as other antihypertensive drugs and has a safety profile similar to placebo. The potent renin inhibitor aliskiren directly inhibits the RAAS system at its rate limiting step and differently from other RAAS blockers; it decreases plasma renin activity (PRA). Although the relationship of increased PRA levels and cardiovascular risk has been shown, it is unclear if the PRA decrease provided by aliskiren has an impact on clinical outcomes and cardiovascular endpoints. On the other hand, large trials like ASPIRE, AVANT-GARDE, ALTITUDE, ASTRONAUT, which investigated the combination of aliskiren with other RAAS blockers, failed to show the expected outcomes or resulted with an increased incidence of adverse effects, which raised more questions. As a result of the ALTITUDE trial, combination of aliskiren with an ACEi or ARB is not recommended in patients with hypertension and diabetes, or at least moderate renal dysfunction. Trials designed to prove aliskiren's efficacy in new indications like diabetes, may face similar problems related to dual RAAS blockade because in the majority of cases, the optimal treatment is achieved with an ACEi or ARB. In this conjuncture, the increase in adverse events seen with aliskiren might be related to dual RAAS blockade rather than aliskiren directly. For instance, it is unclear whether the adverse event incidence would be the same, less, or higher if ALTITUDE was designed to investigate ACEi and ARB combination without aliskiren. In fact, every new molecular entity and mechanism of action faces the same barriers. For the time being, differentiating points like PRA lowering effects as an add-on therapy to calcium channel blockers or hydrochlorothiazide, and the populations that might have additional benefit, should be carefully investigated.

Renal sympathetic denervation for treatment of resistant hypertension: Egyptian experience.

Among the Egyptian population with essential hypertension, a minority are under control (systolic pressure <140 mmHg and diastolic pressure <90 mmHg), despite the use of multiple antihypertensive medications. In this article, we describe our experience with percutaneous treatment using renal artery radiofrequency (RF) ablation. To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension in Egyptian patients. Patients with essential hypertension unresponsive to at least 3 types of antihypertensive medical therapy (baseline office systolic blood pressure ≥160 mmHg) (n = 55) were enrolled between February 2012 and June 2013 and received percutaneous RF ablation. Patients were followed up for 6 months after treatment to detect any change in office-based measurement of blood pressure. Urine and blood samples were taken to evaluate the effects on renal function. A reduction of mean office blood pressure was seen from 174/103 ± 9/5 mmHg at baseline to 150/91 ± 8/5 mmHg at 6 months follow-up (P = 0.001). Also, we noted a significant decrease in plasma renin activity (3.66 ± 0.64 vs. 3.37 ± 0.47 ng/mL per hour; P = 0.003), and there were no periprocedural complications, no adverse events, and no change in renal function during the follow-up period. Also, no change was noted in the number of medications after 6 months (3.95 ± 1.64 vs. 3.67 ± 0.72; P = 0.27). In this observational study, catheter-based renal denervation causes sustained blood pressure reduction in patients with resistant hypertension, without serious adverse events.

Effect of Add‐on Aliskiren to Type 1 Angiotensin Receptor Blocker Therapy on Endothelial Function and Autonomic Nervous System in Hypertensive Patients With Ischemic Heart Disease

The aim of this study was to evaluate the add-on effect of aliskiren to valsartan on endothelial-dependent vasodilation in hypertensive patients with ischemic heart disease (IHD). After 4 weeks of treatment with 80 mg of valsartan, 28 patients were allocated to either continued treatment with valsartan or an add-on treatment with valsartan plus 150 mg of aliskiren. Aliskiren significantly decreased plasma renin activity, whereas endothelium-dependent vasodilation measured by flow-mediated dilation (FMD) did not change. In contrast, heart rate significantly decreased (73.1 ± 9.8 to 66.3 ± 7.0 beats per minute at baseline and 24 weeks, respectively [P = .009]) and the standard deviation of the R-R intervals (SDNN) significantly increased in the aliskiren group. The add-on aliskiren to valsartan therapy may not improve endothelial functions, although it significantly reduced resting heart rate via regulation of the autonomic nervous system in hypertensive patients with IHD.

Catheter-based radiofrequency renal sympathetic denervation for resistant hypertension: initial Egyptian experience

To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension. In a subpopulation of patients with essential hypertension, therapeutic targets are not met, despite the use of multiple types of medication. In this paper we describe our first experience with a novel percutaneous treatment modality using renal artery radiofrequency (RF) ablation. Thirty patients with essential hypertension unresponsive to at least three types of antihypertensive medical therapy (baseline office systolic blood pressure ⩾160 mmHg) were selected between March and September 2012 and received percutaneous RF ablation. Patients were followed up for 6 months after treatment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Another thirty patients were taken as control. A reduction of mean office blood pressure was seen from 170/102 ± 9/5 mmHg at baseline to 151/91 ± 8/6 mmHg at 6 months follow-up ( p = 0.001). Also, we noted a significant decrease in plasma renin activity (3.66 ± 0.64 versus 3.37 ± 0.47 ng/mL/h; p = 0.003). No periprocedural complications, adverse events or change in renal function were noted during follow-up. Catheter-based renal denervation seems an attractive minimally invasive treatment option in patients with resistant hypertension, with a low risk of serious adverse events.

Catheter-based radiofrequency renal sympathetic denervation for resistant hypertension; initial Egyptian experience

To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension. In a subpopulation of patients with essential hypertension, therapeutic targets are not met, despite the use of multiple types of medication. In this paper we describe our first experience with a novel percutaneous treatment modality using renal artery radiofrequency (RF) ablation. Thirty patients with essential hypertension unresponsive to at least three types of antihypertensive medical therapy (baseline office systolic blood pressure ⩾160 mmHg) were selected between March and September 2012 and received percutaneous RF ablation. Patients were followed up for 6 months after treatment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Another thirty patients were taken as control. A reduction of mean office blood pressure was seen from 170/102 ± 9/5 mmHg at baseline to 151/91 ± 8/6 mmHg at 6 months follow-up ( p = 0.001). Also, we noted a significant decrease in plasma renin activity (3.66 ± 0.64 versus 3.37 ± 0.47 ng/mL/h; p = 0.003). No periprocedural complications, adverse events or change in renal function were noted during follow-up. Catheter-based renal denervation seems an attractive minimally invasive treatment option in patients with resistant hypertension, with a low risk of serious adverse events.

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