Cardiovascular Diseases ; drug therapy ; Humans ; Renin ; antagonists & inhibitors

Recently several kinds of new antihypertensive agents were introduced. Diuretics such as indapamide, metyrazone and eprelerone have less side effects compared to thiazide, and have an effect in renal insufficiency. Carvedilol, combined alpha- and beta- adrenergic blocker, has a vasodilating property and an effect on heart failure. The lipid soluble third generation calcium antagonists such as amlodipine, lacidipine and lercardipine are slow onset and long acting and have less side effects, which provide continued effect even if daily doses are missed. Multiple angiotensin converting inhibitors and angiotensin receptor blockers, and the specific aldosterone antagonist eprenolone to block renin-angiotensin-aldosterone system are now available. Additionally new class antihypertensive drugs such as the vasopeptidase inhibitor, the endothelin receptor blocker and the renin inhibitor have been under investigation and shown favorable clinical results, and will be available for clinical use soon.
Adrenergic Antagonists ; Aldosterone ; Amlodipine ; Angiotensin Receptor Antagonists ; Angiotensins ; Antihypertensive Agents ; Calcium ; Diuretics ; Heart Failure ; Hypertension* ; Indapamide ; Receptors, Endothelin ; Renal Insufficiency ; Renin ; Renin-Angiotensin System

Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Atrial Fibrillation ; prevention & control ; Humans ; Mineralocorticoid Receptor Antagonists ; therapeutic use ; Renin-Angiotensin System

Osteopontin (OPN) is a secreted phosphoprotein that is constitutively expressed in the normal kidney and is induced by various experimental and pathologic conditions. Several possible functions of OPN have been suggested, however the mechanism and significance of OPN expression are still uncertain. Since high salt concentration or salt crystal have been known to enhance OPN expression in intact kidney or cultured renal cells, in the present study we examined whether or not a low salt condition had an effect on OPN expression in the kidney. Adult male Sprague-Dawley rats were fed either a normal sodium or a sodium deficient diet for 1 week. Kidneys were processed for in situ hybridization using a digoxigenin-labeled riboprobe and for immunohistochemistry using antibodies to OPN, renin, and Na-K-ATPase. In rats fed a normal sodium diet, OPN mRNA and protein were expressed only in the descending thin limbs of Henle's loop (DTL) and in the papillary and pelvic surface epithelium (PSE). In rats fed a sodium deficient diet, there was a marked decrease in OPN immunoreactivity in the DTL, but no changes in PSE. In contrast, no changes were observed in OPN mRNA expression in the DTL by in situ hybridization, indicating that decreased OPN protein expression was a result of translational regulation. As expected, rats fed a sodium deficient diet were associated with increased immunoreactivity for Na-K-ATPase and renin compatible with activation of the renin-angiotensin system. These results suggest that dietary sodium may be involved in the regulation of OPN expression in the DTL of the rat kidney.
Animal ; Diet, Sodium-Restricted* ; Immunohistochemistry ; In Situ Hybridization ; Kidney/metabolism* ; Male ; Na(+)-K(+)-Exchanging ATPase/metabolism ; Rats ; Rats, Sprague-Dawley ; Renin/metabolism ; Sialoglycoproteins/metabolism ; Sialoglycoproteins/antagonists & inhibitors* ; Sodium/deficiency*

Therapeutic manipulation of the renin-angiotensin-aldosterone system (RAAS) is an important strategy for improving hypertension, diabetes, cardiovascular disease, and chronic kidney disease. Development of hyperkalemia after the administration of RAAS inhibitors is of particular concern because patients at highest risk for this complication are often the same patients who derive the greatest cardiovascular or renoprotective benefit. Based on an overview of the incidence of hyperkalemia during treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers alone and in combination, this review suggests approaches for monitoring, detecting, and managing hyperkalemia in patients treated with RAAS inhibitors. Although the incidence of hyperkalemia with RAAS inhibitors is generally low, hyperkalemia can be associated with increased mortality. When using RAAS inhibitors, it is important to monitor on-treatment electrolyte levels and renal function parameters in patients with a high risk for hyperkalemia.
Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Cardiovascular Diseases ; Humans ; Hyperkalemia ; Hypertension ; Incidence ; Organothiophosphorus Compounds ; Peptidyl-Dipeptidase A ; Renal Insufficiency, Chronic ; Renin-Angiotensin System

The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1–7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1–7)/Mas receptor and ACE2/Ang-(1–9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.
Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Cell Proliferation ; Fibrosis* ; Hemodynamics ; Humans ; Hypertension, Portal* ; Inflammation ; Liver Cirrhosis ; Mineralocorticoid Receptor Antagonists ; Receptors, Angiotensin ; Renin-Angiotensin System* ; Sodium ; Vasoconstriction ; Vasodilation

Angiotensin Receptor Antagonists ; therapeutic use ; Betacoronavirus ; Cardiovascular Diseases ; complications ; drug therapy ; Coronavirus Infections ; complications ; Humans ; Pandemics ; Pneumonia, Viral ; complications ; Renin-Angiotensin System ; drug effects

The physiological roles of brain angiotensin II in mediating water deprivation-induced drinking and in regulating renal renin release were assessed in male Sprague-Dawley rats. Specific AT1 receptor antagonists, losartan and SK 1080, and antisense oligonucleotide (AS-ODN) directed to AT1 receptor mRNA were intracerebroventricularly (i.c.v.) administered in conscious unrestrained rats. When water was given 20 min after i.c.v. injection of AT1 receptor antagonists in 48-h water-deprived rats, losartan and SK 1080 produced approximatly 20% and 50% decrease in 1-h water intake, respectively. In contrast, i.c.v. treatment of the AS-ODN to AT1 receptor mRNA for 24-h did not alter 1-h water intake in 24-h water-deprived rats, but prevented the increase in overnight water intake after 24-h water-deprivation. Six-day i.c.v. treatment of AS-ODN did not alter either the basal plasma renin concentration or renal cortical levels of renin and renin mRNA. The present results suggest that endogenous brain Ang II plays an important role in thirst and water intake through AT1 receptors, but further studies are required to elucidate its regulatory role in renal renin synthesis.
Angiotensin II* ; Angiotensin Receptor Antagonists* ; Angiotensins* ; Animals ; Brain* ; Drinking* ; Humans ; Losartan ; Male ; Negotiating ; Plasma ; Rats* ; Rats, Sprague-Dawley ; Receptors, Angiotensin* ; Renin* ; RNA, Messenger ; Thirst ; Water

INTRODUCTION: Anthracycline is a cornerstone in the treatment of various cancers. One major limitation to its use is cardiotoxicity. Renin angiotensin system (RAS) inhibitors have been shown to attenuate myocardial injury, initial data is promising in its use as prophylaxis for anthracyclineinduced cardiotoxicity. The aim of the study is to determine effectiveness of prophylactic RAS inhibitors in preventing anthracycline-induced cardiotoxicity and adverse cardiac events among adult cancer patients

METHODS: Systematic search of databases PUBMED, MEDLINE, EMBASE, and CENTRAL was done. Selection criteria were: 1) randomized controlled trials (RCT) 2) adult cancer patients with normal ejection fraction and without heart failure symptoms 3) RAS inhibitors as prophylaxis versus placebo 4) development of cardiac events, all-cause mortality and left ventricular ejection fraction (LVEF) reduction as outcomes. Two reviewers independently assessed the trials. Disagreements were resolved with a third reviewer. Test for effect of intervention, heterogeneity, trial quality and risk of bias were assessed using the Cochrane Review Manager Software version 5.3.

RESULTS: Five RCTs involving 530 adult patients, with average age of 50± two years old, and average follow-up from six months to three years were included. Combined clinical outcomes of heart failure, cardiac events and all-cause mortality showed an RR of 0.27[95%CI 0.18, 0.40],p<0.00001, in favor of RAS inhibitors. There is same benefit in LVEF preservation with mean difference of 4.37%[95%CI 1.20, 7.55;p=0.007]. Exploratory subgroup analysis showed significant benefit in LVEF preservation with combined RAS inhibitor and beta-blocker, with mean difference of 2.45%[95%CI 1.27, 3.63]. There is overall significant heterogeneity (I2=95%). Excluding one article with high-risk population, after sensitivity analysis, showed same benefit but reduced heterogeneity.

CONCLUSION: Renin angiotensin system (RAS) inhibitors may be used as prophylaxis for cardiotoxicity. As prophylaxis, it reduced the clinical outcome of cardiac events, heart failure, and all-cause mortality among cancer patients needing anthracycline. Combined RAS inhibitor and betablocker limits LVEF reduction.

Human ; Male ; Female ; Cardiotoxicity ; Renin-angiotensin System ; Medline ; Stroke Volume ; Patient Selection ; Follow-up Studies ; Anthracyclines ; Pubmed ; Heart Failure ; Adrenergic Beta-antagonists ; Neoplasms

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; COVID-19 ; Humans ; Hypertension/drug therapy* ; Renin-Angiotensin System ; Retrospective Studies