scholarly journals Renin–angiotensin–aldosterone system blockade with telmisartan prevents the decline in cardiac contractility orchiectomy-dependent in SHR: role of PPAR-γ activation

Author(s):  
Marito Afonso Sousa Costa Silva ◽  
Camila Almenara ◽  
Antonio Marcos Birocale ◽  
Renata Andrade Ávila ◽  
Ivanita Stefanon ◽  
...  

Abstract The present study aimed to investigate the beneficial role of AT1 receptor blockade and PPAR-γ activation in preventing cardiac contractile changes in hypertensive animals (SHR) with testosterone deficiency. Rats were divided into a control group (sham), orchiectomized (OCT), orchiectomized that received telmisartan (OCT + Tel) or telmisartan plus PPAR-γ antagonist (OCT + Tel + BADGE). After 8 weeks, contractility of isolated papillary muscles was evaluated. The OCT group showed a reduction in the contraction force, avoided in the OCT + Tel and Tel + BADGE groups. Post-pause potentiation (PPP) was similar in the Sham, OCT and OCT + Tel group, suggesting prevention of sarcoplasmic reticulum activity. In contrast, PPP in the OCT + Tel + BADGE group decreased. The reduction in response to calcium or isoproterenol in the OCT group was prevented in the OCT + Tel and Tel + BADGE group. The influx of calcium, assessed indirectly, although it was similar in the OCT and Sham groups, increased both in the OCT + Tel groups and in the OCT + Tel + BADGE groups. SERCA2a protein expression was increased in the OCT group, which was avoided in the OCT + Tel and Tel + BADGE group. NCX expression was increased in the Tel + BADGE group compared to OCT + Tel and sham. Our results suggest that AT1 receptor blockade with telmisartan prevents compromised papillary muscle contractility in SHR. Moreover, it has been shown that the activation of PPAR-γ adds benefits to the inhibition of renin-angiotensin system with telmisartan in preventing harmful effects on the contractility of hypertensive rats with testosterone deficiency.

2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.


1997 ◽  
Vol 136 (6) ◽  
pp. 656-660 ◽  
Author(s):  
Cipriano Garcia del Rio ◽  
María Rosario R Moreno ◽  
Antonio Osuna ◽  
Juan de Dios Luna ◽  
Joaquín García-Estañ ◽  
...  

Abstract Objective: We evaluated the influence of chronic blockade of the renin-angiotensin system on hypertension induced by long-term thyroxine (T4) administration. To this end, we determined the effects of chronic treatment with captopril on blood pressure, cardiac hypertrophy and other renal and metabolic variables of hypertensive hyperthyroid rats. Methods: T4 was administered s.c. at 0·38 μmol/kg per day and captopril was given in the drinking water (1·38 mmol/l). Both treatments were maintained for 6 weeks. Control rats received tap water. After the treatment period, the rats were placed in metabolic cages. Later, blood pressure was measured in conscious rats by intra-arterial determination. Results: T4-treated rats showed an increased mean arterial pressure (MAP) whereas, in rats treated with T4 plus captopril, MAP was similar to that of the control group. Captopril did not affect the increased heart rate or ventricular weight/body weight ratio of hyperthyroid rats, but it improved the reduced creatinine clearance of these animals. Conclusions: The elevation in blood pressure produced by long-term T4 administration was prevented by chronic blockade of the renin-angiotensin system. Captopril improved the renal function of hyperthyroid rats, but did not affect the relative cardiac hypertrophy of these animals. European Journal of Endocrinology 136 656–660


2007 ◽  
Vol 9 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Kouichi Tamura ◽  
Yutaka Tanaka ◽  
Yuko Tsurumi ◽  
Koichi Azuma ◽  
Atsu-Ichiro Shigenaga ◽  
...  

1996 ◽  
Vol 117 (5) ◽  
pp. 891-901 ◽  
Author(s):  
J.P. Kats ◽  
L.M.A. Sassen ◽  
A.H.J. Danser ◽  
M.P.J. Polak ◽  
L.K. Soei ◽  
...  

2001 ◽  
Vol 21 (6) ◽  
pp. 580-592 ◽  
Author(s):  
Arnold Boonstra ◽  
Dick de Zeeuw ◽  
Paul E. de Jong ◽  
Gerjan Navis

2020 ◽  
Vol 27 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Izabela Guimarães Barbosa ◽  
Giulia Campos Ferreira ◽  
Diomildo Ferreira Andrade Júnior ◽  
Cássio Rocha Januário ◽  
André Rolim Belisário ◽  
...  

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.


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