Renin-angiotensin System In Control Research Articles

Plant-food-derived Bioactives in Managing Hypertension: From Current Findings to Upcoming Effective Pharmacotherapies.

A sedentary lifestyle has evoked a high risk of cardiovascular (CV) disease, diabetes, and obesity, all of them with high morbimortality rates and with a common denominator, hypertension. Numerous pharmacological drugs have been used for the treatment of hypertension. However, the side effects associated with the use of existing pharmacological therapies have triggered a demand for plant-based medications. In this connection, the aim of this review was to provide an in-depth analysis of the use of plant-derived bioactives for the effective management of hypertension. Phytoconstituents from leaves, bark, stem, roots, seeds, and fruits of medicinal plants grown in our different regions of the globe have been highly searched. Among them, polyphenols (e.g., flavonoids as quercetin, anthocyanins as cyanidin, tannins as ellagic acid, stilbenes as resveratrol, lignans as honokiol and others as hydroxytyrosol or curcumin), organosulfur compounds (e.g. s-allyl cysteine and allicin), fatty acids (e.g. α-lipoic acid, DHA and oleic acid), alkaloids (e.g. berberine or tetrandrine) and some terpenes have been intensively investigated for the management of hypertension, with effective ability being stated in controlling high blood pressure and related health problems both in vivo and in vitro studies. Some of the activities presented by these bioactive compounds are reducing oxidative stress, renin-angiotensin system control, SIRT1 activation, regulating platelet aggregation and COX activity, anti-atherogenic effects, anti-inflammatory properties, vasorelaxation and other results that translate into the prevention or control of hypertension. The knowledge of these bioactive compounds is important in developing countries where traditional medicine is the majority, but it can also give rise to new approaches in hypertension therapy.

The 24-h pattern of dgcr8, drosha, and dicer expression in the rat suprachiasmatic nuclei and peripheral tissues and its modulation by angiotensin II.

Study was focused on regulatory interactions between the circadian system and the renin-angiotensin system in control of microRNA (miRNA) biosynthesis. Responsiveness of the miRNA biosynthetic pathway, selected pre-miRNAs and clock genes to angiotensin II (AngII) infusion was analysed in the suprachiasmatic nuclei (SCN), liver, kidney and heart during a 24-h cycle. per2 exerted a rhythmic expression profile in all analysed tissues. clock expression showed a rhythmic pattern in the peripheral tissues with tissue-specific response to AngII. dgcr8 expression showed a tissue-specific rhythm only in peripheral tissues, which diminished in the heart and kidney after AngII delivery. Expression of pre-miR-30c was rhythmic in all studied peripheral tissues, pre-miR-34a expression exerted significant rhythm only in the liver. AngII delivery increased expression of pre-miR-30c and pre-miR-34a in the kidney. To conclude, peripheral oscillators are more likely to exhibit rhythmic miRNA biosynthesis responsive to AngII in a tissue-specific manner compared to SCN.

A Randomized Controlled Trial of Angiotensin-Converting Enzyme Inhibition for Skeletal Muscle Dysfunction in COPD

BACKGROUND:Skeletal muscle impairment is a recognized complication of COPD, predicting mortality in severe disease. Increasing evidence implicates the renin-angiotensin system in control of muscle phenotype. We hypothesized that angiotensin-converting enzyme (ACE) inhibition would improve quadriceps function and exercise performance in COPD.METHODS:This double-blind, randomized placebo-controlled trial investigated the effect of the ACE inhibitor, fosinopril, on quadriceps function in patients with COPD with quadriceps weakness. Primary outcomes were change in quadriceps endurance and atrophy signaling at 3 months. Quadriceps maximum voluntary contraction (QMVC), mid-thigh CT scan of the cross-sectional area (MTCSA), and incremental shuttle walk distance (ISWD) were secondary outcomes.RESULTS:Eighty patients were enrolled (mean [SD], 65 [8] years, FEV1 43% [21%] predicted, 53% men). Sixty-seven patients (31 fosinopril, 36 placebo) completed the trial. The treatment group demonstrated a significant reduction in systolic BP (Δ−10.5 mm Hg; 95% CI, −19.9 to −1.1; P = .03) and serum ACE activity (Δ−20.4 IU/L; 95% CI, −31.0 to −9.8; P < .001) compared with placebo. No significant between-group differences were observed in the primary end points of quadriceps endurance half-time (Δ0.5 s; 95% CI, −13.3-14.3; P = .94) or atrogin-1 messenger RNA expression (Δ−0.03 arbitrary units; 95% CI, −0.32-0.26; P = .84). QMVC improved in both groups (fosinopril: Δ1.1 kg; 95% CI, 0.03-2.2; P = .045 vs placebo: Δ3.6 kg; 95% CI, 2.1-5.0; P < .0001) with a greater increase in the placebo arm (between-group, P = .009). No change was shown in the MTCSA (P = .09) or ISWD (P = .51).CONCLUSIONS:This randomized controlled trial found that ACE inhibition, using fosinopril for 3 months, did not improve quadriceps function or exercise performance in patients with COPD with quadriceps weakness.TRIAL REGISTRY:Current Controlled Trials; No.: ISRCTN05581879; URL: www.controlled-trials.com

S48 The Effect of Angiotensin-Converting Enzyme Inhibition on Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease: A Randomised Controlled Trial

IntroductionSkeletal muscle impairment is a well recognised complication of COPD, predicting mortality in severe disease.1 Evidence from animal models, genetic studies and observational cohorts suggest a role for the renin-angiotensin...

The effects of cilazapril and valsartan on the mRNA and protein expressions of atrial calpains and atrial structural remodeling in atrial fibrillation dogs

Owing to relative inefficacy and side effects of currently available antiarrhythmic drugs, current interest has shifted to treatments that target atrial fibrillation (AF) substrate. It has been suggested that calpain-induced atrial structural remodelling is under the control of renin-angiotensin system during AF. The purpose of this study is to investigate the effects of cilazapril and valsartan on the mRNA and protein expression of atrial calpains and atrial structural remodelling in AF dogs induced by chronic rapid atrial pacing. Twenty-seven dogs were randomly divided into sham-operated group (n = 6), control group (n = 7), cilazapril group (n = 7) and valsartan group (n = 7). One thin silicon plaque containing 4 pairs of electrodes was sutured to each atrium. A pacemaker was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the right atrial appendage. The dogs in control group, cilazapril group and valsartan group were paced at 400 beats per minutes for 6 weeks. The dogs in cilazapril and valsartan groups received cilazapril (1mg x kg(-1)x d(-1)) or valsartan (30mg x kg(-1) x d(-1)) 1 week before rapid atrial pacing until pacing stop respectively. Transthoracic and transoesophageal echocardiographic examinations were performed in order to detect the changes of left atrium volume and contractile function. The inducibility and duration of AF were measured in all the groups. The expressions of atrial calpain I and calpain II mRNA were semi-quantified by reverse transcription-polymerase chain reaction. The protein levels of calpain I and calpain II in atrial myocardium were measured by Western-blot method. Pathohistological and ultrastructural changes in atrial tissue were tested by light and electron microscopy. Compared with the sham-operated control group, dramatic smaller left atrium and left atrial appendage volumes and significant higher atrial contractile function were observed in the cilazapril and valsartan groups. After 6-week atrial tachy-pacing, the mRNA and protein expressions of calpain I increased dramatically in the control group than that in the sham group, tissue calpain protein expression in all groups significantly correlated with the myolysis (r = 0.89, P < 0.01). Cilazapril and valsartan could significantly inhibit the gene and protein expressions of calpain I. No differences were found in the expression of calpain II mRNA and protein between the groups. Compared with atrial myocytes obtained from sham dogs, atrial myocytes from the control group dogs showed a reduced number of sarcomeres, a significant higher myolytic area of atria (24.3% vs. 3.1%, P < 0.01), increased vacuolization and dissolution. Cilazapril and valsartan could effectively prevent the pathohistological and ultrastructural changes induced by chronic rapid atrial pacing, dramatically decrease the area of myolysis (P < 0.05) and significantly reduce the inducibility and duration of AF. The expression of calpain I mRNA and protein increased remarkably in AF dogs. Cilazapril and valsartan can inhibit calpain I up-regulation, suppress atrial structural remodeling, and prevent the induction and promotion of AF in chronic rapid atrial pacing dogs.

Effect of manipulation of the renin-angiotensin system in control of drinking in juvenile Atlantic salmon (Salmo salar L) in fresh water and after transfer to sea water.

Drinking in Atlantic salmon (Salmo salar) juveniles was investigated in fresh water and following transfer to sea water. There was a significant effect of fish size on drinking, and smolts (20-30 g) imbibed about ten times less water than alevins of 0.2-0.3 g. Freshwater smolts drank at a rate of 0.15 +/- 0.03 ml.kg-1.h-1 and administration of doses of 10 or 20 mg.kg-1 of papaverine (stimulator of the renin-angiotensin system RAS) or [Asn1, Val5]-Angiotensin II (0.4 mumol.kg-1) resulted in significant increases in drinking, while administration of the angiotensin converting enzyme inhibitor, enalapril (50 mg.kg-1) had no effect on drinking. Transfer of Atlantic salmon smolts to 1/3, 2/3 and full strength sea water resulted in significant increases in drinking to 1.06 +/- 0.12, 1.24 +/- 0.0.16 and 3.89 +/- 0.28 ml.kg-1.h-1, respectively. In sea water, stimulation of the endogenous RAS by administration of papaverine (20 mg.kg-1) resulted in a 20% increase in drinking, while administration of enalapril to doses of 50 and 200 mg.kg-1 lowered drinking to 1.99 +/- 0.48 and 0.32 +/- 0.06 ml.kg-1.h-1, respectively. All treatments were without effect on blood plasma levels of Na+ and Cl- in fresh water, while in sea water smolts both stimulation and inhibition of drinking resulted in hemoconcentration of Na+ and Cl-. The role of the renin angiotensin system in control of drinking and hydromineral balance in Atlantic salmon is discussed.

Drinking in Freshwater-Adapted Rainbow Trout Fry, Oncorhynchus mykiss (Walbaum), in Response to Angiotensin I, Angiotensin II, Angiotensin-Converting Enzyme Inhibition, and Receptor Blockade

Drinking in freshwater-adapted rainbow trout fry was investigated in response to the administration of angiotensin I, angiotensin II, the angiotensin II antagonist saralasin, and the angiotensin-converting enzyme inhibitor enalapril. Rainbow trout fry (0. 8-1.5 g), as previously shown, drank at a rate of about 0.7-0.9 mL kg⁻¹ h⁻¹ in freshwater, and the intramuscular administration of angiotensin I or angiotensin II increased drinking rates maximally to about 4-5 mL kg⁻¹ h-1', while intraperitoneal injections at a similar dose were less potent. Intramuscular administration of increasing levels of angiotensin II (0.2-2 nmol g⁻¹ of [Asn¹, Val⁵]-angiotensin II) resulted in a dose-dependent increase of drinking rate, and this response was partially but significantly inhibited by the administration of the angiotensin II receptor blocker saralasin ([Sar¹, Val⁵, Ala⁸]-angiotensin II). Drinking rates were also increased (maximally to about 5 mL kg⁻¹ h⁻¹) in response to intramuscular injection of increasing levels of angiotensin I, with maximum responses between 0.26 and 0.35 nmol⁻¹ g, and this response was significantly lowered by the administration of enalapril and by saralasin. The administration of losartan (DuP 753), a selective inhibitor of the receptor subtype AT, in mammals, had an inconsistent effect on drinking in freshwater and seawater-adapted fish. Although the role of drinking in juvenile freshwater fish is not understood, the present results constitute further evidence for the involvement of the renin-angiotensin system in control of drinking in fish.

Role of the renin-angiotensin system in potassium control.

To determine the importance of the renin-angiotensin system in control of plasma potassium concentration and excretion, potassium control was studied in two groups of dogs in response to a 20-fold increase in sodium intake (from 10 to 200 meq/day). Group I was intact whereas group II lacked feedback control of the renin-angiotensin system, which was eliminated by continuous infusion of 10 ng . kg-1 . min-1 angiotensin II. This rate of infusion reduced endogenous plasma renin activity (PRA) to undetectable levels throughout the study. The sodium forcing did not result in measurable changes in plasma potassium concentration or excretion in group I, in which PRA fell to 40% and plasma aldosterone concentration (PAC) to 60% of the low sodium levels. In group II the same sodium forcing produced a 12% decrease in plasma potassium concentration and a 79% increase in urinary potassium excretion. PAC also fell to 60% of the low sodium level in group II. The results demonstrate the importance of the renin-angiotensin system as a link between the nephron and the zona glomerulosa that is essential in controlling plasma potassium concentration and excretion during changes in sodium balance.

ROLE OF RENIN IN ADAPTATION TO SEA WATER IN EURYHALINE FISHES

The role of the renin-angiotensin system as an aldosterone stimulating factor in the mammal is well-established (1, 2). A high salt intake diminishes the demand to conserve sodium in the body, and the secretion of aldosterone is decreased by the control of renin-angiotensin system. Decreased renin activity on a high salt diet has been shown in the mammal (3-5). In 1942, Friedman, Kaplan, and Williams found the absence of renin in the kidney of marine fish, but detected it in the fresh water fish (6). If this be true, renin-angiotensin would play a role in salt adaptation of the fish. We kept Japanese eels in both fresh and sea water for 3 to 11 weeks, and determined the renin content of the kidney, to see if euryhalinity is controlled by renin in eels. We found a decrease in renin of those kept in sea water, and suggested that the renin-angiotensin system plays a part in salt adaptation (7). The purpose of this paper is to give details of these studies on Japanese eels and other euryhaline fishes adapted to sea water.

Clinical Aspects of Adrenal Function

Dr. Mills has done an admirable job in accomplishing the task which he has set out for himself. He states in the preface that the book is intended for medical students and for doctors who are not experts in the adrenal field, and that a certain amount of dogmatism is necessary to maintain simplicity of presentation. The book makes no attempt to give reference to the vast literature in this field but, instead, reflects chiefly the author's considerable experience. His own prejudice is reflected by the general underplay of the renin angiotensin system in control of aldosterone secretion and emphasis on corticoid secretion rates. Many clinical endocrinologists would take exception to the statement that 4,000 roentgens delivered to the pituitary may interfere with other pituitary functions and should not, therefore, be given to young patients. In spite of these minor defects, the author has written a small volume that is