scholarly journals Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS) in Rats with Thyroid Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Susan A. S. Farhadi ◽  
Kawa F. Dizaye
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Positive Control ◽  
Urine Flow ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Group 6 ◽  
Renin Level ◽  
Excretion Rates

Background and Objectives. Thyroid hormones have an important role in the growth and development of various tissues including the kidney, which is the major site of renin release and the consequent angiotensin and aldosterone formation. Therefore any derangement in thyroid function can result in abnormal functioning in the renin-angiotensin-aldosterone system. The current study was undertaken to find the impact of using a direct renin inhibitor (Aliskiren) and an angiotensin-converting enzyme inhibitor (Fosinopril) on the components of the renin-angiotensin-aldosterone system (RAAS) in rats with thyroid dysfunctions. Method. Forty-two male albino rats were divided into three subgroups. First group (6 rats) served as control. Second group (18 rats) served as hyperthyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Third group (18 rats) served as hypothyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Induction of hyperthyroidism and hypothyroidism was done through daily oral administration of L-Thyroxine and Propylthiouracil, respectively. On day 40 of the study, the rats were sacrificed and blood was collected for estimation of renin, angiotensin I, angiotensin II, aldosterone, TSH, T3, and T4. The collected blood samples were also used for estimation of levels blood urea, serum creatinine, liver enzymes, and serum electrolytes. Blood pressure and urine collection were done on days 1 and 40. The collected urine was used for estimation of urine flow, sodium excretion, and potassium excretion rates. Results. In hypothyroid induced rats, serum renin level dropped as expected, while the use of Aliskiren and Fosinopril on these hypothyroid rats raised renin level due to the feedback mechanism. Both angiotensin I and II were significantly (P <0.05) lower than normal levels in the hypothyroid rats, unlike the level of aldosterone, which was higher than normal level. There was nonsignificant lowering in BP (systolic, diastolic, and mean BP) in the hypothyroid rats. Treatment of these rats with Aliskiren and Fosinopril did not lower the blood pressure more than normal when compared to the hypothyroid group. The hypothyroid rats also showed a decrease in level of serum creatinine. In hyperthyroid rats, there was a rise in levels of serum renin, angiotensin II, and aldosterone; nevertheless, the increase in angiotensin I level was significant. The use of Aliskiren and Fosinopril increased the level of renin nonsignificantly (decreased angiotensin I significantly). Hyperthyroid rats showed a significant increase in systolic, diastolic, and mean blood pressure. Both Aliskiren and Fosinopril increased urine flow, Na+   excretion, and K+ excretion rates. Aliskiren was better at reducing the high blood pressure. Conclusion. Aliskiren and Fosinopril in hyperthyroid rats decreased serum angiotensin I, angiotensin II, and aldosterone. Blockade of renin and inhibition of angiotensin-converting enzyme both resulted in a rebound increase in level of renin in hypothyroid rats. Aliskiren is better at controlling blood pressure in hyperthyroid rats. Urine flow, sodium excretion, and potassium excretion rates were improved by the use of Aliskiren and Fosinopril in hyperthyroid rats.

scholarly journals PERAN KOMPLEKS JUKSTAGLOMERULUS TERHADAP RESISTENSI PEMBULUH DARAH

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Renny M. Toreh ◽  
Sonny J.R. Kalangi ◽  
Sunny Wangko
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Sodium Intake ◽  
Angiotensin Receptor Blockers ◽  
Antihypertensive Agents ◽  
Angiotensin I ◽  
Renin Angiotensin ◽  
Renin Synthesis ◽  
Receptor Blockers

Abstract: As the main structural component of the renin-angiotensin-aldosterone system (RAAS), the juxtaglomerular complex plays a very important role in the regulation of vascular resistance. The synthesis and release of renin into the circulation occurs due to the decrease of blood pressure, loss of body fluid, and a decrease of sodium intake. Renin converts angiotensinogen into angiotensin I, which is further converted by the angiotensin converting enzyme (ACE) into angiotensin II. This angiotensin II causes vasoconstriction of blood vessels, resulting in an increase of vascular resistance and blood pressure. The ACE inhibitors and the angiotensin receptor blockers (ARBs) do not inhibit the RAAS completely since they cause an increase of renin activity. The renin blockers are more effective in inhibiting RAAS activity; therefore, these renin blockers can be applied as antihypertensive agents with fewer side effects. The RAAS activity can be inhibited by a decrease of renin synthesis in the juxtaglomerular complex by blocking the signals in the juxtaglomerular complex that stimulate renin synthesis, and by blocking the gap junctions in the juxtaglomerular complex. Keywords: juxtaglomerular complex, vascular resistance, RAAS.   Abstrak: Kompleks jukstaglomerulus sebagai komponen struktural utama sistem renin angiotensin berperan penting dalam pengaturan resistensi pembuluh darah. Sintesis dan pelepasan renin ke sirkulasi terjadi karena tekanan darah yang rendah, kehilangan cairan tubuh, dan kurangnya intake natrium. Renin akan memecah angiotensinogen menjadi angiotesin I yang kemudian secara cepat dikonversi oleh enzim pengonversi angiotensin  menjadi angiotensin II. Angiotensin II menyebabkan vasokontriksi pembuluh darah sehingga meningkatkan resistensi pembuluh darah yang pada akhirnya akan meningkatkan tekanan darah. ACEinhibitor dan ARB kurang sempurna dalam menghambat kerja SRAA oleh karena keduanya memutuskan rantai mekanisme timbal balik sehingga meningkatkan aktifitas renin. Penghambat renin lebih efektif digunakan untuk menghambat aktifitas SRAA sehingga penghambat renin dapat digunakan sebagai obat anti-hipertensi dan memiliki efek samping yang rendah. Metode penghambatan SRAA yang juga dapat dikembangkan ialah penghambatan sintesis renin dalam kompleks jukstaglomerulus dengan cara menekan sinyal-sinyal dalam kompleks jukstaglomerulus yang merangsang sintesis renin dan menghambat fungsi taut kedap yang terdapat dalam kompleks jukstaglomerulus. Kata kunci: kompleks juksta glomerulus, resistensi vaskular, SRAA.

scholarly journals Renin-angiotensin-aldosterone system inhibitors – a realm of confusion in COVID-19

2021 ◽  
Vol 4 (Special2) ◽  
pp. 389-394
Author(s):  
Angela Madalina Lazar
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Current Knowledge ◽  
Angiotensin Receptor Blockers ◽  
Protective Effects ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Raas Inhibitors

Currently, there is a persisting dispute regarding the renin-angiotensin-aldosterone-system (RAAS) inhibitors' safety of use in COVID-19 pandemics. On one side, RAAS inhibitors appear to determine an overexpression of ACE2, the receptor of SARS-CoV-2. Therefore, they could increase the risk of SARS-CoV-2 infection and its degree of severity. On the other side, the discontinuation of RAAS leads to cardiovascular decompensation and has been discouraged by the major medical societies. Also, large-cohort studies report beneficial or at least neutral effects for the RAAS inhibitors in COVID-19 patients. Worldwide, millions of patients receive RAAS inhibitors for the treatment of hypertension and other important comorbidities. In this context, knowledge of the exact effect of these medications becomes of crucial significance. This paper aims to fill in a gap in the current knowledge and presents a putative mechanism by which RAAS inhibitor administration's beneficial results can be explained better. RAAS inhibitors can be beneficial, as they counteract the excessive detrimental activation of the classical angiotensin-converting enzyme (ACE) axis, decreasing the angiotensin II levels. The angiotensin receptor blockers (ARBs) increase the angiotensin II levels, while the angiotensin-converting enzyme inhibitors (ACEI) increase the angiotensin I levels; these substrates will compete with the SARS-CoV-2 for the ACE2 binding, decreasing the viral infectivity. In addition, following the RAAS inhibitors treatment, the up-regulated ACE2 will cleave these substrates (angiotensin I and II), particularly to angiotensin 1-7 that possesses vasodilator, protective effects.

scholarly journals COMPARATIVE EFFICACY OF BLOCKADE OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM WITH COMBINATIONS OF ALISKIREN AND AMLODIPINE, RAMIPRIL AND AMLODIPINE IN PATIENTS WITH ESSENTIAL HYPERTENSION

2017 ◽  
pp. 24-29
Author(s):  
E. Krutikov ◽  
S. Chistyakova ◽  
V. Gorbatuk
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Combined Therapy ◽  
Control Group ◽  
Common Disease ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Daily Average ◽  
Group I

Hypertension is one of the most common disease of the cardiovascular system. Important components of a rational antihypertensive therapy are drugs that block the RAAS. The aim of the study was to conduct a comparative evaluation of the effectiveness of blockade of the renin-angiotensin-aldosterone system with drug combinations – aliskiren and amlodipine and combination of ramipril and amlodipine in patients with hypertension and increased body weight. 50 patients with hypertension of stage II, II degree, high and very high risk were involved in the study. Patients were randomized into two groups depending on the received treatment. The first group (25 patients) consisted of patients treated with combined therapy including ramipril and amlodipine, the second group (25 patients) consisted of patients receiving a combination of aliskiren and amlodipine. The control group (25 people) included apparently healthy people. By the 12th week of the study the daily average systolic blood pressure in the first group was 146 (145; 150) mm Hg and 131 (130; 137) mm Hg in the second group, respectively, the daily average diastolic blood pressure was equal to 94 (91; 96) mm Hg in the first group and 81 (80; 82) mm Hg in the second group . By the 12th week of treatment plasma renin levels in the first group was equal to 73 (50; 78) and 15 (14; 27) in the second group, respectively, the level of angiotensin-I in the first group was 6 (4; 7) and 1,4 (1,1; 1,9) in the second group, aldosterone levels in the first group was equal to 134 (132; 145) and 130 (123; 132) in the second group, respectively. It is found that combination of aliskiren and amlodipine have the advantage over the combination of ramipril and amlodipine in achieving of purposeful level of systolic and diastolic blood pressure in patients with hypertension and overweight. The purposeful level of blood pressure reached to 56,6% of patients in group I and 80% of patients in group II to 12th week of the study. Receiving both combinations equally reduces plasma aldosterone levels at the same time receiving a combination of aliskiren and amlodipine accompanied by a decrease in plasma rennin level of 69% and angiotensin-I of 67%, while the combination of ramipril and amlodipine increases of these hormones on 68% and 65% respectively. Thus, using combination of ramipril and amlodipine more effective in patients with low rennin hypertension , patients with normal and high rennin hypertension necessary combination of aliskiren and amlodipine.

Response of Blood Pressure and the Renin—Angiotensin—Aldosterone System to Chronic Ambulatory Peritoneal Dialysis in Hypertensive End-Stage Renal Failure

1982 ◽  
Vol 63 (s8) ◽  
pp. 207s-209s ◽  
Author(s):  
Ph. Glasson ◽  
H. Favre ◽  
M. B. Vallotton
Keyword(s):  
Blood Pressure ◽  
Peritoneal Dialysis ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
End Stage ◽  
Chronic Ambulatory Peritoneal Dialysis

1. Chronic ambulatory peritoneal dialysis allows good control of blood pressure in patients with hypertensive end-stage renal disease. The role of the renin-angiotensin-aldosterone system has therefore been studied in seven patients during the first 6 months of chronic ambulatory peritoneal dialysis treatment. 2. Steady increases in plasma renin activity and aldosterone were observed with a good correlation between these two variables. Plasma electrolytes, renin substrate and body weight did not change significantly. 3. Angiotensin II perfusion tests, performed at the end of the study, showed a relative vascular resistance to angiotensin II. 4. Stimulation of the renin-angiotensin-aldosterone system may be partially explained by this last observation or by removal of an unknown vasopressor substance responsible for the inhibition of the plasma renin activity.

scholarly journals Serum ACE-2, angiotensin II, and aldosterone levels are unchanged in patients with COVID-19

2020 ◽  
Author(s):  
Marina Rieder ◽  
Luisa Wirth ◽  
Luisa Pollmeier ◽  
Maren Jeserich ◽  
Isabella Goller ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Serum Levels ◽  
Host Cells ◽  
Control Group ◽  
Serum Samples ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
And Control

Abstract Background The role of the renin-angiotensin-aldosterone system in COVID-19 is controversially discussed. SARS-CoV-2 enters host cells by binding to angiotensin-converting enzyme 2 and activity of the renin-angiotensin-aldosterone system may affect susceptibility to SARS-CoV-2 infection and outcome of patients with COVID-19. Methods In this prospective single-center study, we determined the serum levels of ACE-2, angiotensin II and aldosterone in patients with COVID-19 compared to control patients presenting with similar symptoms in the emergency unit. Results We analyzed serum samples from 24 SARS-CoV-2 positive and 61 SARS-CoV-2 negative patients. SARS-CoV-2 positive and control patients did not differ in baseline patients characteristics, symptoms and clinical presentation. Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group. In line with this, serum potassium as surrogate parameter for RAAS activity and blood pressure were similar in both groups. Conclusions In summary, we did not find evidence for altered RAAS activity including angiotensin II, aldosterone, or potassium levels, and blood pressure in patients with COVID-19.

scholarly journals Novel angiotensin peptides regulate blood pressure, endothelial function, and natriuresis.

1998 ◽  
Vol 9 (9) ◽  
pp. 1716-1722
Author(s):  
C M Ferrario ◽  
M C Chappell ◽  
R H Dean ◽  
S N Iyer
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Receptor Subtype ◽  
Angiotensin I ◽  
Blood Pressure Lowering Effect ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Pressure Lowering

Accumulating evidence suggests that angiotensin-(1-7) is an important component of the renin-angiotensin system, having actions that are either identical to or opposite that of angiotensin II. Angiotensin I can be directly converted to angiotensin-(1-7), bypassing formation of angiotensin II. This pathway is under the control of three enzymes: neutral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptidase 24.26. Two of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to the breakdown of bradykinin and the atrial natriuretic peptide. Furthermore, angiotensin-(1-7) is a major substrate for angiotensin-converting enzyme. These observations suggest that the process of biotransformation between the various Ang peptides of the renin-angiotensin system and other vasodepressor peptides are intertwined through this enzymatic pathway. Substantial evidence suggests that angiotensin-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, and nitric oxide, while also augmenting the metabolic actions of bradykinin. In addition, angiotensin-(1-7) alters tubular sodium and bicarbonate reabsorption, decreases Na+-K+-ATPase activity, induces diuresis, and exerts a vasodilator effect. These physiologic effects of angiotensin-(1-7) favor a blood pressure-lowering effect. The majority of the data currently available suggest that angiotensin-(1-7) mediates its effects through a novel non-AT1/AT2 receptor subtype.

scholarly journals Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury

2021 ◽  
Author(s):  
Davide Ventura ◽  
Amy L Carr ◽  
R Duane Davis ◽  
Scott Silvestry ◽  
Linda Bogar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Ii Receptor ◽  
Pulmonary Tissue ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Membrane Bound ◽  
Raas Inhibitors ◽  
Novel Coronavirus

Abstract It has been established SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocytes pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) in the current pandemic. ACE2 serves as regulatory enzyme in maintaining homeostasis between proinflammatory Angiotensin II and anti-inflammatory Angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome (ARDS). Augmentation of the ACE2/Ang1,7 axis represent a critical target in the supportive management of COVID-19 associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats

1984 ◽  
Vol 62 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Ernesto L. Schiffrin ◽  
Jolanta Gutkowska ◽  
Gaétan Thibault ◽  
Jacques Genest
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Ace Inhibition ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.

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