Encapsulation of Carvedilol in Nanomicelles Improves Central Hemodynamics and Target Organ Damage Protection in Spontaneously Hypertensive Rats

Figures

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  FIGURE 1. Measurement of cardiomyocyte surface area in LV slices stained with hematoxylin–eosin. Cardiomyocyte surface area in LV of Wistar Kyoto rats (WKY rats) and spontaneously hypertensive rats after 8‐week treatment with vehicle (SH rats), 15 mg/kg carvedilol‐LCF (CAR‐LCF), 10 mg/kg losartan solution (LOS), or 15 mg/kg carvedilol Soluplus‐NMs (CAR‐NMs), (n = 6 for all experimental groups). Data are shown as mean ± SEM. Differences in variables among groups were tested using one‐way analysis of variance (ANOVA) followed by Bonferroni test. *p < 0.05 versus WKY rats, #p < 0.05 versus SH rats, &p < 0.05 versus CAR‐LCF, •p < 0.05 versus CAR‐NMs. LV, left ventricle.

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  FIGURE 2. Estimation of ICF in LV slices stained with Picrosirius Red. ICF (%) in LV of Wistar Kyoto rats (WKY rats) and spontaneously hypertensive rats after 8‐week treatment with vehicle (SH rats), 15 mg/kg carvedilol‐LCF (CAR‐LCF), 10 mg/kg losartan solution (LOS), or 15 mg/kg carvedilol Soluplus‐NMs (CAR‐NMs), (n = 6 for all experimental groups). Data are shown as mean ± SEM. Differences in variables among groups were tested using one‐way analysis of variance (ANOVA) followed by Bonferroni test. *p < 0.05 versus WKY rats, #p < 0.05 versus SH rats, &p < 0.05 versus CAR‐LCF, •p < 0.05 versus CAR‐NMs. ICF, interstitial collagen fraction; LV, left ventricle.

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  FIGURE 3. Estimation of ICF in thoracic aorta rings stained with Picrosirius Red. ICF (%) in rings of thoracic aorta from Wistar Kyoto rats (WKY rats) and spontaneously hypertensive rats after 8‐week treatment with vehicle (SH rats), 15 mg/kg carvedilol‐LCF (CAR‐LCF), 10 mg/kg losartan solution (LOS), or 15 mg/kg carvedilol Soluplus‐NMs (CAR‐NMs), (n = 6 for all experimental groups). Data are shown as mean ± SEM. Differences in variables among groups were tested using one‐way analysis of variance (ANOVA) followed by Bonferroni test. *p < 0.05 versus WKY rats, #p < 0.05 versus SH rats, &p < 0.05 versus CAR‐LCF. ICF, interstitial collagen fraction; LV, left ventricle.

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  FIGURE 4. Estimation of thoracic aorta wall thickness in aorta rings stained with hematoxylin–eosin. Aortic wall thickness of Wistar Kyoto rats (WKY rats) and spontaneously hypertensive rats after 8‐week treatment with vehicle (SH rats), 15 mg/kg carvedilol‐LCF (CAR‐LCF), 10 mg/kg losartan solution (LOS), or 15 mg/kg carvedilol Soluplus‐NMs (CAR‐NMs), (n = 6 for all experimental groups). Data are shown as mean ± SEM. Differences in variables among groups were tested using one‐way analysis of variance (ANOVA) followed by Bonferroni test. *p < 0.05 versus WKY rats, #p < 0.05 versus SH rats.

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  FIGURE 5. Proinflammatory cytokines expression levels in LV measured by Western Blot. Levels of TNF‐a (A) and IL‐6 (B) in the LV of Wistar Kyoto (WKY rats) and spontaneously hypertensive rats after 8‐week treatment with vehicle (SH rats), 15 mg/kg carvedilol‐LCF (CAR‐LCF), 10 mg/kg losartan solution (LOS), or 15 mg/kg carvedilol Soluplus‐NMs (CAR‐NMs), (n = 6 for all experimental groups). Data are shown as mean ± SEM. Differences in variables among groups were tested using one‐way analysis of variance (ANOVA) followed by Bonferroni test. *p < 0.05 versus WKY rats, #p < 0.05 versus SH rats. AU, arbitrary units; LV, left ventricle.

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  FIGURE 6. TGF‐β expression levels in the LV measured by Western Blot. Levels of TGF‐β in the LV of Wistar Kyoto (WKY rats) and spontaneously hypertensive rats after 8‐week treatment with vehicle (SH rats), 15 mg/kg carvedilol‐LCF (CAR‐LCF), 10 mg/kg losartan solution (LOS), or 15 mg/kg carvedilol Soluplus‐NMs (CAR‐NMs), (n = 6 for all experimental groups). Data are shown as mean ± SEM. Differences in variables among groups were tested using one‐way analysis of variance (ANOVA) followed by Bonferroni test. *p < 0.05 versus WKY rats, #p < 0.05 versus SH rats, •p < 0.05 versus CAR‐NMs. AU, arbitrary units; LV, left ventricle.

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  FIGURE 7. CAR plasma levels determined by RP‐HPLC. Plasma levels of carvedilol were measured after a single oral administration of 15 mg/kg CAR‐LCF or CAR‐NMs. Data are shown as mean ± SEM.