AT<sub>1</sub>Receptor Blockade Improves Myocardial Functional Performance in Obesity

Oliveira-Junior, Silvio Assis de; Muzili, Nayara de Araújo; Carvalho, Marianna Rabelo de; Ota, Gabriel Elias; Morais, Camila Souza de; Vieira, Larissa Fregapani da Costa; Ortiz, Mateus Oliveira; Campos, Dijon H. S.; Cezar, Marcelo Diacardia Mariano; Okoshi, Marina Politi; Okoshi, Katashi; Cicogna, Antonio C.; Martinez, Paula Felippe

doi:10.36660/abc.20190131

Silvio Assis de Oliveira-Junior

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

https://orcid.org/0000-0002-8895-9456

Nayara de Araújo Muzili

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

Marianna Rabelo de Carvalho

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

https://orcid.org/0000-0001-9789-2487

Gabriel Elias Ota

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

Camila Souza de Morais

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

Larissa Fregapani da Costa Vieira

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

Mateus Oliveira Ortiz

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

Dijon H. S. Campos

Faculdade de Medicina de Botucatu – UNESP, Botucatu, SP - Brazil

https://orcid.org/0000-0002-4933-0604

Marcelo Diacardia Mariano Cezar

Faculdade de Ciências Sociais e Agrárias de Itapeva (FAIT), Itapeva, SP - Brazil

Universidade Estadual de São Paulo (UNESP), Departamento de Medicina Interna, Botucatu, SP - Brazil

https://orcid.org/0000-0003-4829-9606

Marina Politi Okoshi

Universidade Estadual de São Paulo (UNESP), Departamento de Medicina Interna, Botucatu, SP - Brazil

https://orcid.org/0000-0001-7728-4505

Katashi Okoshi

Universidade Estadual Paulista Júlio de Mesquita Filho - Faculdade de Medicina - Campus de Botucatu, Botucatu, SP - Brazil

Antonio C. Cicogna

Faculdade de Medicina de Botucatu – UNESP, Botucatu, SP - Brazil

https://orcid.org/0000-0002-4402-6523

Paula Felippe Martinez

Universidade Federal de Mato Grosso do Sul, Campo Grande, MS – Brazil

https://orcid.org/0000-0001-9477-3386

Mailing Address: Silvio Assis de Oliveira-Junior • Federal University of Mato Grosso do Sul - Laboratory of Striated Muscle Study (LEME) - Av. Costa e Silva, s/n Cidade Universitária Campo Grande, MS – Brazil E-mail: oliveirajr.ufms@gmail.com, silvio.oliveira-jr@ufms.br

Author contributions

Conception and design of the research: Oliveira-Junior SA, Okoshi MP, Martinez PF; Acquisition of data: Muzili NA, Carvalho MR, Ota GE, Morais CS, Vieira LFC, Ortiz MO, Campos DHS, Cezar MDM, Okoshi K; Analysis and interpretation of the data: Oliveira-Junior SA, Campos DHS, Cezar MDM, Okoshi MP, Okoshi K, Cicogna AC, Martinez PF; Statistical analysis and writing of the manuscript: Oliveira-Junior SA; Obtaining financing: Oliveira-Junior SA, Martinez PF; Critical revision of the manuscript for intellectual content: Okoshi MP, Okoshi K, Cicogna AC, Martinez PF.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures (4)
Tables (2)

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Figure 1
– Functional papillary muscle assessment at baseline with extracellular [Ca²⁺] equal to 2.5 mM; results in mean±SD; (A) DT: maximum developed tension; (B) +dT/dt: maximum DT variation speed; (C) –dT/dt: maximum DT decrease; CO: Control group; OB: Obese group; CL: Control Losartan group; OL: Obese Losartan group. * p<0.05 compared to CO; Two-Way ANOVA and Tukey Test.

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Figure 2
– Functional papillary muscle assessment according to extracellular calcium concentration (1.0-2.5 mM). Results expressed regarding the baseline with extracellular [Ca²⁺] equal to 0.5 mM value (mean±SD); (A) DT: maximum developed tension; (B) +dT/dt: maximum positive DT change; (C) -dT/dt, maximum DT decrease. CO: Control group; CL: Control Losartan group; OB: Obese group; OL: Obese Losartan group. Group’s effect: † p<0.05 compared to OB; ‡ p<0.05 compared to CL. Calcium’s Effect: §, p<0.05 compared to 1.0 mM; ¶, p<0.05 compared to 1.5 mM; Two-Way RM ANOVA and Bonferroni Test.

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Figure 3
– Isolated papillary muscle assessement, according to post-pause potentiation (PPP) time. Results are expressed regarding the baseline with extracellular [Ca²⁺] equal to 0.5 mM value (mean±SD); (A) DT: maximum developed tension; (B) +dT/dt: maximum positive DT change; (C) –dT/dt: maximum DT decrease; CO: Control group; CL: Control Losartan group; OB: Obese group; OL: Obese Losartan group. PPP’s effect: §, p<0.05 compared to 30s; Group’s effect: * p<0.05 vs CO; † p<0.05 compared to OB; ‡ p<0.05 compared to CL. Two-Way RM ANOVA and Bonferroni Test.

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Figure 4
– Functional assessment of the isolated papillary muscle, according to Isoproterenol concentration. Results expressed regarding the baseline with extracellular [Ca²⁺] equal to 1.0 mM value (mean±SD); (A) DT: maximum developed tension; (B) +dT/dt: maximum positive DT change; (C) -dT/dt: maximum DT decrease; CO: Control group; OB: Obese group; CL: Control Losartan group; OL: Obese group under Losartan. Group’s effect: * p<0.05 compared to C; ‡ p<0.05 compared to CL. Isoproterenol’s Effect: §, p<0.05 compared to Baseline; ¶, p<0.05 vs 0.1 mM; Two-Way RM ANOVA and Bonferroni Test.

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Table 1
– Mean and standard deviation of nutritional variables, murinometry and cardiac morphology according with group

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Table 2
– Mean and standard deviation of systolic blood pressure, measures of structure and functional performance of the heart analyzed by echocardiogram and left ventricular tissue Doppler, according to group and time of assessment

Variable		Group

		CO	OB	CL	OL
Nutritional Profile	Body weight (g)	451 ± 58	507 ± 64 *	456 ± 49	517 ± 50^‡
	Caloric intake (Kcal)	81.9 ± 8.2	80.7 ± 7.5	80.3 ± 9.2	78.7 ± 7.9
	Total intake of unsaturated lipids (g)	122 ± 12	235 ± 22 *	120 ± 14	230 ± 23^‡
	Total intake of saturated lipids (g)	196 ± 20	433 ± 40 *	193 ± 22	422 ± 43^‡
	Feed efficiency (%)	26.82 ± 2.11	32.22 ± 4.38 *	28.43 ± 0.94	35.12 ± 4.78^‡
	Adiposity (%)	3.48 ± 0.73	5.19 ± 1.47 *	3.61 ± 1.27	5.50 ± 1.48^‡
Cardiac Morphology	Atria (g)	0.096 ± 0.015	0.113 ± 0.015 *	0.092 ± 0.009	0.100 ± 0.022^†
	Atria/ Tibia (mg/mm)	2.22 ± 0.33	2.59 ± 0.35 *	2.15 ± 0.21	2.29 ± 0.46^†
	RVW (g)	0.231 ± 0.029	0.241 ± 0.030	0.230 ± 0.039	0.245 ± 0.040
	RVW/Tibia (mg/mm)	5.36 ± 0.68	5.50 ± 0.70	5.34 ± 0.79	5.64 ± 0.86
	LVW (g)	0.844 ± 0.083	0.950 ± 0.099	0.800 ± 0.082 *	0.799 ± 0.087^†
	LVW/Tibia (mg/mm)	19.6 ± 1.7	21.7 ± 2.4 *	18.7 ± 1.5	18.4 ± 1.7^†

Variable	Moment	Group

		CO	OB	CL	OL
SBP (mmHg)	16th Wks	119.4 ± 9.2	133.3 ± 12.3 *	119.5 ± 9.4	132.0 ± 9.6^‡
SBP (mmHg)	20th Wks	129.6 ± 9.3	139.3 ± 12.6	103.0 ± 13.2 *^§	107.7 ± 7.4^{† §}
HR (bpm)	16th Wks	277 ± 41	272 ± 27	276 ± 48	273 ± 44
HR (bpm)	20th Wks	285 ± 32	266 ± 39	265 ± 39	277 ± 39
LA (mm)	16th Wks	5.47 ± 0.79	5.80 ± 0.60	5.87 ± 0.74	5.81 ± 0.89
LA (mm)	20th Wks	5.69 ± 0.56	5.95 ± 0.55	5.70 ± 0.60	5.77 ± 0.67
LA/AO	16th Wks	1.37 ± 0.18	1.45 ± 0.14	1.48 ± 0.14	1.42 ± 0.18
LA/AO	20th Wks	1.42 ± 0.16	1.44 ± 0.10	1.40 ± 0.11	1.42 ± 0.12
LVDT (mm)	16th Wks	1.317 ± 0.072	1.374 ± 0.044	1.313 ± 0.071	1.361 ± 0.058
LVDT (mm)	20th Wks	1.272 ± 0.067^§	1.305 ± 0.043^§	1.262 ± 0.085^§	1.271 ± 0.061^§
LVDD (mm)	16th Wks	7.95 ± 0.64	7.91 ± 0.37	7.80 ± 0.57	7.82 ± 0.44
LVDD (mm)	20th Wks	8.11 ± 0.41	8.15 ± 0.26	8.06 ± 0.54	8.08 ± 0.52
LVDD/ Tibia (mm/mm)	16th Wks	0.184 ± 0.015	0.180 ± 0.008	0.182 ± 0.012	0.180 ± 0.007
LVDD/ Tibia (mm/mm)	20th Wks	0.188 ± 0.010	0.186 ± 0.007	0.188 ± 0.011	0.187 ± 0.012
LVSD (mm)	16th Wks	3.65 ± 0.68	3.56 ± 0.39	3.54 ± 0.65	3.69 ± 0.56
LVSD (mm)	20th Wks	3.66 ± 0.42	3.55 ± 0.50	3.86 ± 0.67	3.75 ± 0.62
PWSV (mm/s)	16th Wks	40.44 ± 4.70	43.63 ± 2.95	42.31 ± 5.11	39.29 ± 3.96
PWSV (mm/s)	20th Wks	42.92 ± 4.45	48.72 ± 4.81 *^§	42.82 ± 3.60	47.96 ± 4.03^{‡ §}
EF	16th Wks	0.900 ± 0.039	0.907 ± 0.023	0.903 ± 0.037	0.892 ± 0.037
EF	20th Wks	0.907 ± 0.022	0.914 ± 0.033	0.887 ± 0.039	0.898 ± 0.037
ES (%)	16th Wks	54.32 ± 6.38	55.00 ± 3.72	54.83 ± 6.28	52.92 ± 5.41
ES (%)	20th Wks	54.94 ± 3.58	56.49 ± 5.67	52.34 ± 5.73	53.83 ± 5.45
E/A	16th Wks	1.65 ± 0.35	1.49 ± 0.25	1.52 ± 0.25	1.43 ± 0.23
E/A	20th Wks	1.60 ± 0.33	1.50 ± 0.23	1.74 ± 0.27	1.39 ± 0.26^‡
EDT (ms)	16th Wks	50.09 ± 6.85	49.50 ± 4.56	47.64 ± 8.69	51.10 ± 6.19
EDT (ms)	20th Wks	47.64 ± 7.47	50.58 ± 6.59	50.17 ± 5.84	54.40 ± 5.77
IVRT	16th Wks	58.88 ± 6.98	58.12 ± 4.22	55.38 ± 7.72	54.66 ± 5.26
IVRT	20th Wks	53.60 ± 4.22	52.47 ± 4.87	53.49 ± 7.17	52.72 ± 3.78
S’(cm/s)	16th Wks	3.57 ± 0.31	3.79 ± 0.28	3.72 ± 0.24	3.79 ± 0.45
S’(cm/s)	20th Wks	4.00 ± 0.24^§	4.05 ± 0.47	3.91 ± 0.29	4.19 ± 0.27^§
E’ (cm/s)	16th Wks	4.62 ± 0.53	4.23 ± 0.40	4.25 ± 0.39	4.04 ± 0.53
E’ (cm/s)	20th Wks	4.85 ± 0.57	4.80 ± 0.32^§	4.83 ± 0.38^§	4.92 ± 0.52^§
A’ (cm/s)	16th Wks	3.75 ± 0.86	3.85 ± 0.59	3.78 ± 0.83	3.49 ± 0.50
A’ (cm/s)	20th Wks	4.37 ± 0.87	3.78 ± 1.08	3.61 ± 0.75 *	4.31 ± 0.81^§
E/E’	16th Wks	16.80 ± 3.62	18.76 ± 3.13	18.12 ± 2.27	18.86 ± 2.61
E/E’	20th Wks	17.89 ± 2.59	18.79 ± 2.35	17.27 ± 1.52	17.22 ± 2.51

[1] Mailing Address: Silvio Assis de Oliveira-Junior • Federal University of Mato Grosso do Sul - Laboratory of Striated Muscle Study (LEME) - Av. Costa e Silva, s/n Cidade Universitária Campo Grande, MS – Brazil E-mail: oliveirajr.ufms@gmail.com, silvio.oliveira-jr@ufms.br

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