scholarly journals AT1 receptor antagonism but not mineralocorticoid receptor blockade lowers blood pressure in obese Zucker rats

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Jussara M Carmo ◽  
Alexandre A Silva ◽  
John E Hall
Keyword(s):  
Blood Pressure ◽  
Mineralocorticoid Receptor ◽  
At1 Receptor ◽  
Zucker Rats ◽  
Receptor Blockade ◽  
Receptor Antagonism ◽  
Obese Zucker Rats ◽  
Mineralocorticoid Receptor Blockade

Effects of brain mineralocorticoid receptor blockade on blood pressure and renal functions in DOCA–salt hypertension

2002 ◽  
Vol 436 (3) ◽  
pp. 207-216 ◽  
Author(s):  
Kamal Rahmouni ◽  
Rosana M. Sibug ◽  
E.Ronald De Kloet ◽  
Mariette Barthelmebs ◽  
Michèle Grima ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mineralocorticoid Receptor ◽  
Receptor Blockade ◽  
Renal Functions ◽  
Salt Hypertension ◽  
Mineralocorticoid Receptor Blockade

scholarly journals Impact of Mineralocorticoid Receptor And Angiotensin Ii Type 1 Receptor Antagonism on Blood Pressure Regulation in Obese Zucker Rats: Role of Sex Differences

2020 ◽  
Author(s):  
Jussara M do Carmo ◽  
Alexandre A da Silva ◽  
John E Hall
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Mineralocorticoid Receptor ◽  
Combined Treatment ◽  
Zucker Rats ◽  
Male And Female ◽  
Obese Zucker Rats ◽  
Males And Females

Abstract Background Previous studies suggest that obesity-induced hypertension in females, but not males, is due to leptin-mediated stimulation of aldosterone secretion and subsequent activation of the mineralocorticoid receptor (MR). Although angiotensin II type 1 receptor (AT1R) antagonism lowers blood pressure (BP) in male obese Zucker rats (OZR), which have defective leptin signaling, the potential role of sex differences in BP responses to RAAS blockade, including MR antagonism, in obesity is still unclear. We tested the cardiovascular effects of MR antagonism, alone or in combination with AT1R blockade in male and female OZR (n=5/sex) and lean Zucker rats (LZR, n=7/sex). Methods BP and heart rate (HR) were measured by telemetry 24-hrs/day. After a 6-day control period, spironolactone (40 mg/kg/day) was given for 10 days followed by a 7-day combined treatment with losartan (20 mg/kg/day), and followed by 6-day post-treatment recovery period. Results Compared to lean rats, OZR were hypertensive (Mean arterial pressure: 115±4 vs. 104±2 and 111±s vs. 100±3 mmHg for males and females) and had lower HR (355±9 vs. 393±7 and 367±10 vs. 412±13 bpm). MR blockade alone did not alter BP or HR in lean or obese male and female Zucker rats, whereas combined treatment reduced BP in obese and lean rats by 31±3 vs. 21±1 and 8±1 vs. 5±1 mmHg in males and females, respectively. No changes were observed in HR. Conclusions These results suggest that there are important sex differences in BP responses to chronic AT1R blockade but no major involvement of MR activation in BP regulation in OZR.

scholarly journals The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260554
Author(s):  
C. J. Leader ◽  
G. T. Wilkins ◽  
R. J. Walker
Keyword(s):  
Myocardial Infarction ◽  
Mineralocorticoid Receptor ◽  
Cardiac Fibrosis ◽  
Interstitial Fibrosis ◽  
Kidney Tissue ◽  
Macrophage Infiltration ◽  
Receptor Blockade ◽  
Receptor Antagonism ◽  
Mineralocorticoid Receptor Antagonism ◽  
Mineralocorticoid Receptor Blockade

Aims The renin-angiotensin-aldosterone axis plays a key role in mediating cardiac and kidney injury. Mineralocorticoid receptor antagonism has beneficial effects on cardiac dysfunction, but effects are less well quantified in the cardiorenal syndrome. This study investigated cardiac and kidney pathophysiology following permanent surgical ligation to induce myocardial infarction (MI) in hypertensive animals with or without mineralocorticoid receptor antagonism. Methods Hypertension was induced in adult male Cyp1a1Ren2 rats. Hypertensive animals underwent MI surgery (n = 6), and were then treated daily with spironolactone for 28 days with serial systolic blood pressure measurements, echocardiograms and collection of urine and serum biochemical data. They were compared to hypertensive animals (n = 4), hypertensive animals treated with spironolactone (n = 4), and hypertensive plus MI without spironolactone (n = 6). Cardiac and kidney tissue was examined for histological and immunohistochemical analysis. Results MI superimposed on hypertension resulted in an increase in interstitial cardiac fibrosis (p<0.001), renal cortical interstitial fibrosis (p<0.01) and glomerulosclerosis (p<0.01). Increased fibrosis was accompanied by myofibroblast and macrophage infiltration in the heart and the kidney. Spironolactone post-MI, diminished the progressive fibrosis (p<0.001) and inflammation (myofibroblasts (p<0.05); macrophages (p<0.01)) in both the heart and the kidney, despite persistently elevated SBP (182±19 mmHg). Despite the reduction in inflammation and fibrosis, spironolactone did not modify ejection fraction, proteinuria, or renal function when compared to untreated animals post MI. Conclusion This model of progressive cardiorenal dysfunction more closely replicates the clinical setting. Mineralocorticoid receptor blockade at a clinically relevant dose, blunted progression of cardiac and kidney fibrosis with reduction in cardiac and kidney inflammatory myofibroblast and macrophage infiltration. Further studies are underway to investigate the combined actions of angiotensin blockade with mineralocorticoid receptor blockade.

ACE Inhibition and AT1 Receptor Blockade Prevent Fatty Liver and Fibrosis in Obese Zucker Rats

Obesity ◽  
2008 ◽  
Vol 16 (4) ◽  
pp. 770-776 ◽  
Author(s):  
Jorge E. Toblli ◽  
Marina C. Muñoz ◽  
Gabriel Cao ◽  
José Mella ◽  
Lisandro Pereyra ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Ace Inhibition ◽  
At1 Receptor ◽  
Zucker Rats ◽  
Receptor Blockade ◽  
Obese Zucker Rats
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