Pharmacological interventions into the renin–angiotensin system with ACE inhibitors and angiotensin II receptor antagonists: effects beyond blood pressure lowering

Düsing, Rainer

doi:10.1177/1753944716644130

Cited by 27 publications

(19 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32 Accordingly, many AT1R blockers (ARBs) are now in clinical use for their anti-hypertensive and to a lesser extent, antifibrotic actions. 33,34 There is evidence that heteromers constitutively form between AT1R and AT2R, with reports suggesting that this impairs AT1R internalization depending on the celltype studied. 35 This may also explain how the AT2R can inhibit the growth effects of the AT1R.…”

mentioning

confidence: 99%

AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis

Chow

Kočan

Shen

et al. 2019

JASN

View full text Add to dashboard Cite

Background Recombinant human H2 relaxin (serelaxin) has emerged as a potential agent to treat fibrosis, the pathological hallmark of chronic disease. As we now know that serelaxin requires the angiotensin II (Ang II) type 2 receptor (AT2R) to ameliorate renal fibrogenesis in vitro and in vivo, we sought to determine if its anti-fibrotic actions were affected by Ang II type 1 receptor (AT1R) modulation. Methods We examined the signal transduction mechanisms of serelaxin when applied to primary rat renal and human cardiac myofibroblasts in vitro, and in three models of renal-or cardiomyopathy-induced fibrosis in vivo. Results The anti-fibrotic signal transduction of serelaxin via its cognate receptor, relaxin family peptide receptor 1 (RXFP1), was abrogated by the AT1R blockers, irbesartan or candesartan in vitro and in vivo. Candesartan also ameliorated serelaxin's anti-fibrotic actions in the left ventricle of mice with cardiomyopathy, indicating that the inhibitory effects of candesartan were not confined to the kidney. In a transfected cell system, we demonstrated that serelaxin did not directly bind to AT1Rs but that constitutive AT1R-RXFP1 interactions could form. To potentially explain these findings, we also demonstrated that all three receptors were expressed by renal and cardiac (myo)fibroblasts and that antagonists acting at each receptor directly/allosterically blocked the anti-fibrotic effects of either serelaxin or the AT2R agonist, Compound 21. Conclusions These findings have significant implications for the concomitant use of RXFP1 or AT2R agonists with AT1R blockers and suggest that functional AT1R-AT2R-RXFP1 interactions on myofibroblasts may represent new targets for controlling fibrosis progression.

show abstract

mentioning

confidence: 99%

AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis

Chow

Kočan

Shen

et al. 2019

JASN

View full text Add to dashboard Cite

show abstract

“…A maior prevalência de uso destes medicamentos no tratamento da HAS também foi encontrada em outros estudos (MIBIELLI et al, 2014;LIMA;MEINERS;SOLER, 2010). A preferência pelos medicamentos que reduzem a atividade do SRAA é justificada pelos efeitos adicionais que estas drogas apresentam como a redução da agregação plaquetária e trombose, redução do remodelamento cardíaco e vascular e efeitos metabólicos protetores cerebrais e renais (DÜSING, 2016). É importante ressaltar, contudo, que a terapia com BRA bloqueia os efeitos da angiotensina II em seus receptores, mas não impede a síntese deste peptídeo vasoconstrictor.…”

Section: Discussionunclassified

Perfil Farmacoterapêutico e Nível de Adesão à Terapia de Pacientes Assistidos pelo Hiperdia, Lagarto-SE

Oliveira

Almeida

Oliveira

et al. 2016

Iniciac cient Cesumar

View full text Add to dashboard Cite

RESUMO:O sucesso da terapia anti-hipertensiva depende dos fármacos utilizados e da adesão do paciente ao tratamento. Por isso, este trabalho objetivou a determinação do perfil farmacoterapêutico e o nível de adesão ao tratamento medicamentoso de hipertensos atendidos pelo Hiperdia de Lagarto-SE. Foram entrevistados 228 pacientes com o auxílio de um questionário para a coleta de variáveis sociodemográficas, econômicas, relacionadas ao estilo de vida, às patologias e às farmacoterapêuticas. A adesão à terapia farmacológica foi determinada pelos testes de Morisky-Green (TMG) e Haynes-Sackett (THS). Os resultados foram analisados pelo teste do Qui-quadrado e exato de Fisher (p<0,05*). A maioria dos pacientes foi do gênero feminino (70,6%), com baixo grau de escolaridade, pertencentes à classe socioeconômica E (49,1%), autodeclarados brancos (44,7%) e com faixa etária entre 51 e 60 anos (37,7%). A prevalência de sobrepeso/obesidade foi de 89,1%. Contudo, um estilo de vida favorável ao controle da pressão arterial foi relatado pela maioria dos entrevistados. A adesão à terapia farmacológica foi encontrada em apenas 31,2% (THS) e 27,2% (TMG) dos hipertensos. O perfil farmacoterapêutico se caracterizou pela monoterapia sendo a losartana (50%) e os inibidores da ECA (18,4%) os mais citados. Maior adesão à terapia foi encontrada nos hipertensos em monoterapia (p=0,016*), que utilizam medicamentos de outras classes terapêuticas (p<0,0001*), que esclarecem suas dúvidas sobre a medicação com farmacêuticos (p=0,016*) e que não realizam consultas médicas para avaliação do anti-hipertensivo usado (p=0,001*). Estes resultados mostram baixa adesão à terapia farmacológica que pode estar associada ao baixo nível socioeconômico e baixo grau de escolaridade. PALAVRAS-CHAVE:Hipertensão Arterial Sistêmica; Teste de Morisky-Green; Teste de Haynes-Sackett; Medicamentos Anti-hipertensivos. FARMACO-THERAPEUTIC PROFILE AND ADHESION LEVEL TO THERAPY BY PATIENTS ATTENDED BY HIPERDIA IN LAGARTO, BRAZILABSTRACT: The success of anti-hypertension therapy depends on the drugs used and on patient´s adhesion to treatment. Current study determines the pharmaco-therapy profile and the adhesion level of treatment of hypertensive patients by HIPERDIA in Lagarto SE Brazil. Two hundred and twenty-eight patients were interviewed by means of a questionnaire to collect socio-demographic and economic variables on life style, pathologies and pharmaco-therapies. Adhesion to pharmacological therapy was determined by the Morisky-Green (TMG) and Haynes-Sackett (THS) tests. Result were analyzed by Chi-square test and Fisher Exact test (p<0.05*). Most patients were female (70.6%), with low schooling and belonged to socio-economic class E (49.1%), white (44.7%) within the 51 -60 year old bracket (37.7%). Prevalence of overweight/obesity was 89.1%. A life-style favorable to arterial pressure control was reported by most interviewees. Adhesion to pharmacotherapy reached only 31.2% (THS) and 27.2% (TMG) of hypertensive people. The pharmaco-therapeutic profile was charac...

show abstract

“…Similarly, superior outcomes over conventional therapy were documented in the R eduction of E ndpoints in N IDDM with the A ngiotensin II A ntagonist L osartan (RENAAL) Study [156] and the I rbesartan D iabetic N ephropathy T rial (IDNT) [168] in subjects with type 2 diabetic nephropathy (Figure 2). As concluded by Düsing [18, 171], improved safety and enhanced tolerability over other therapies may be the greatest clinical advantage of this drug class. However, some have questioned whether ARBs show equivalent efficacy when compared with ACE inhibitors [172].…”

Section: 0 Angiotensin Receptor Blockersmentioning

confidence: 99%

Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease

Ferrario

Mullick

2017

Pharmacological Research

102

View full text Add to dashboard Cite

A collective century of discoveries establishes the importance of the renin angiotensin aldosterone system in maintaining blood pressure, fluid volume and electrolyte homeostasis via autocrine, paracrine and endocrine signaling. While research continues to yield new functions of angiotensin II and angiotensin-(1-7), the gap between basic research and clinical application of these new findings is widening. As data accumulates on the efficacy of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers as drugs of fundamental importance in the treatment of cardiovascular and renal disorders, it is becoming apparent that the achieved clinical benefits is suboptimal and surprisingly no different than what can be achieved with other therapeutic interventions. We discuss this issue and summarize new pathways and mechanisms effecting the synthesis and actions of angiotensin II. The presence of renin-independent non-canonical pathways for angiotensin II production are largely unaffected by agents inhibiting renin angiotensin system activity. Hence, new efforts should be directed to develop drugs that can effectively block the synthesis and/or action of intracellular angiotensin II. Improved drug penetration into cardiac or renal sites of disease, inhibiting chymase –the primary angiotensin II forming enzyme in the human heart–, and/or inhibiting angiotensinogen synthesis would all be more effective strategies to inhibit the system. Additionally, given the role of angiotensin II in the maintenance of renal homeostatic mechanisms, any new inhibitor should possess greater selectivity of targeting pathogenic angiotensin II signaling processes and thereby limit inappropriate inhibition.

show abstract

Pharmacological interventions into the renin–angiotensin system with ACE inhibitors and angiotensin II receptor antagonists: effects beyond blood pressure lowering

Cited by 27 publications

References 84 publications

AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis

AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis

Perfil Farmacoterapêutico e Nível de Adesão à Terapia de Pacientes Assistidos pelo Hiperdia, Lagarto-SE

Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease

Contact Info

Product

Resources

About