Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: General characteristics of experimental animals.

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: Activity Assay

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: The effect of MLN-4760 treatment on the activity of soluble RAS enzymes determined from angiotensin product/substrate ratios in plasma–plasma renin activity, PRA ( a ); soluble angiotensin converting enzyme, ACE-S ( b ); and the total alternative renin angiotensin system activity, Alt-S ( c ).

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: Activity Assay

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: The correlation between the plasma level of the total alternative renin angiotensin system activity (Alt-S) and the weight of the visceral fat ( a ) and body weight ( b ). The correlation between the plasma level of angiotensin 1–7 (Ang 1–7) and the weight of the visceral fat ( c ) and body weight ( d ) in SHRs and SHRs treated with MLN-4760 (SHR + MLN).

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: Activity Assay

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: The effect of MLN-4760 treatment on the integrated pressure responses of the cardiovascular system. The changes in mean blood pressure (ΔMAP) were followed after infusion of acetylcholine (1 µg/kg, ( a )), noradrenaline (1 µg/kg, ( b )), NOS inhibitor (L-NAME, 30 mg/kg, ( c )), ACE inhibitor-captopril (10 mg/kg, ( e )) and H 2 S scavenger bismuth(III) subsalicylate (BSC, 0.25 µg/kg, ( f )). The effect of acetylcholine (1 µg/kg) also was followed before and after pretreatment with L-NAME (30 mg/kg, ( d )). The results are presented as the mean ± S.E.M., and differences between groups were analyzed by Student´s t -test. * p < 0.05, ** p < 0.01 vs. SHR; ++ p < 0.01 vs. SHR + MLN.

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques:

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: Endothelium-dependent vasorelaxant response of the thoracic aorta ( a ), femoral artery ( d ) and mesenteric artery (( g , h )-AUC (area under curve) values). Noradrenaline-induced contractile response of the thoracic aorta (( b )-absolute response, ( c )-percent values of the maximum response), femoral artery (( e )-absolute response, ( f )-percent values of the maximum response) and mesenteric artery (( i )-absolute response). Arteries were isolated from control SHRs and SHRs treated with MLN-4760. The results are presented as the mean ± S.E.M., and differences between groups were analyzed by repeated two-way repeated measures ANOVA or Student´s t -test, as appropriate. * p < 0.05 vs. SHR; # p < 0.05 vs. maximal response to Ach.

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: Isolation

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: The effect of acute Mas receptor inhibition on the endothelium-dependent vasorelaxation ( a ) and contractile response ( b ) of TA isolated from control SHRs and SHRs treated with MLN-4760. The mRNA levels of the Mas1 and ACE2 genes ( c , e ) and the protein expression of the Mas receptor and ACE2 ( d , f ) were measured in aortic tissue. The results are presented as the mean ± S.E.M., and differences between groups were analyzed by three-way ANOVA or Student’s t -test, as appropriate. * p < 0.05 vs. SHRs, ** p < 0.01 vs. SHRs; + p < 0.05, +++ p < 0.001 vs. SHR + MLN.

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: Inhibition, Isolation, Expressing

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: The effect of acute NO synthase (NOS) inhibition on endothelium-dependent vasorelaxation ( a ) and the contractile response ( b ) of TA isolated from control SHRs and SHRs treated with MLN-4760. The total NOS activity ( c ) and the protein expression of endothelial eNOS ( d ), neuronal nNOS ( e ) and inducible iNOS ( f ) were measured in aortic tissue. The results are presented as the mean ± S.E.M., and differences between groups were analyzed by three-way ANOVA or Student´s t -test, as appropriate, * p < 0.05, ** p < 0.01 vs. SHR, *** p < 0.001 vs. SHR; + p < 0.05 vs. SHR + MLN.

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: Inhibition, Isolation, Activity Assay, Expressing

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: The effect of the H 2 S scavenger on endothelium-dependent vasorelaxation ( a ) and the contractile response ( b ) of TA isolated from control SHRs and SHRs treated with MLN-4760. The protein expression of cystathionine γ-lyase CSE ( c ) and cystathionine-β-synthase CBS ( d ) was measured in aortic tissue. The results are presented as the mean ± S.E.M., and differences between groups were analyzed by three-way ANOVA or Student´s t -test, as appropriate. * p < 0.05 vs. SHR, ** p < 0.01 vs. SHR; + p < 0.05 vs. SHR + MLN.

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: Isolation, Expressing

Journal: Biomedicines

Article Title: Vascular Effects of Low-Dose ACE2 Inhibitor MLN-4760—Benefit or Detriment in Essential Hypertension?

doi: 10.3390/biomedicines10010038

Figure Lengend Snippet: MLN-4760 reduces vascularization in the model of chick chorionallantoic membrane, determined as the number of vascular branching points in the area of MLN-4760 application compared to the area adjacent to the area of application ( a ). * p < 0.02 vs. SHR, x p < 0.02 vs. A Appl in the given group. Results are analyzed by two-way ANOVA. Next pictures are examples of chick chorionallantoic membrane in native yellow color with black Teflon circle placed on chick chorionallantoic membrane ( b ), and examples of evaluations of vascular branching in pictures of chick chorioallantoic membrane with colors inverted to blue in the control group ( c ) and in MLN-4760-treated chorioallantoic membranes ( d ) after the removal of Teflon circles. Abbreviations: A Appl , area of drug application; A Adj , area adjacent to area of drug application.

Article Snippet: The specific ACE2 inhibitor MLN-4760 (MLN) (MedChemExpress, Monmouth Junction, NJ, USA) was administered using Alzet ® mini-osmotic pumps, model 2002, with a pumping rate of 0.5 μL/h for 14 days (DurectTM, Cupertino, CA, USA) at a dose of 1 mg/kg/day dissolved in 10% dimethyl sulfoxide in isotonic saline (sodium chloride 0.9% Braun intravenous solution for infusion; 308 mOsm/L; 250 mL; B. Braun Melsungen AG, Germany).

Techniques: