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Different Anti-Contractile Function and Nitric Oxide Production of Thoracic and Abdominal Perivascular Adipose Tissues.

Victorio JA, Fontes MT, Rossoni LV, Davel AP - Front Physiol (2016)

Bottom Line: PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta.However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT.In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas Campinas, Brazil.

ABSTRACT
Divergent phenotypes between the perivascular adipose tissue (PVAT) surrounding the abdominal and the thoracic aorta might be implicated in regional aortic differences, such as susceptibility to atherosclerosis. Although PVAT of the thoracic aorta exhibits anti-contractile function, the role of PVAT in the regulation of the vascular tone of the abdominal aorta is not well defined. In the present study, we compared the anti-contractile function, nitric oxide (NO) availability, and reactive oxygen species (ROS) formation in PVAT and vessel walls of abdominal and thoracic aorta. Abdominal and thoracic aortic tissue from male Wistar rats were used to perform functional and molecular experiments. PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta. Abdominal PVAT exhibited a reduction in endothelial NO synthase (eNOS) expression compared with thoracic PVAT, without differences in eNOS expression in the vessel walls. In agreement with this result, NO production evaluated in situ using 4,5-diaminofluorescein was less pronounced in abdominal compared with thoracic aortic PVAT, whereas no significant difference was observed for endothelial NO production. Moreover, NOS inhibition with L-NAME enhanced the phenylephrine-induced contraction in endothelial-denuded rings with PVAT from thoracic but not abdominal aorta. ROS formation and lipid peroxidation products evaluated through the quantification of hydroethidine fluorescence and 4-hydroxynonenal adducts, respectively, were similar between PVAT and vessel walls from the abdominal and thoracic aorta. Extracellular superoxide dismutase (SOD) expression was similar between the vessel walls and PVAT of the abdominal and thoracic aorta. However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT. In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta. Although relative SOD isoforms are different along the aorta, ROS formation, and lipid peroxidation seem to be similar. These findings highlight the specific regional roles of PVAT depots in the control of vascular function that can drive differences in susceptibility to vascular injury.

No MeSH data available.


Related in: MedlinePlus

Reduced eNOS expression and NO availability in abdominal vs. thoracic perivascular adipose tissue (PVAT). (A) eNOS protein expression in vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. Representative blots and Ponceau S staining were demonstrated at the upper panels of the figure and densitometric analysis is expressed as a fold change of THO expression at the bottom panel. (B) Top panels-Representative fluorographs of 4,5-diaminofluorescein diacetate (DAF-2) signal obtained in transverse sections of vessel walls and PVAT from THO and ABD aortic tissues in the absence (upper panel) and presence (lower panel) of L-NAME. Scale bar = 100 μm (20X objective). Bottom panel-Quantified NO availability, measured as DAF-2 fluorescence intensity in the endothelial layer and PVAT of THO and ABD aorta. (C) Concentration-response curves to phenylephrine in rat thoracic (left panel) and abdominal (right panel) aorta without (−) endothelium (E) and with (+) PVAT in the absence or presence of L-NAME. Data are expressed as the means ± SEM; the number of animals is indicated in the bars or in parenthesis. Student's t-test, P < 0.05: *ABD vs. THO PVAT; Two-way ANOVA, P < 0.05: & PVAT+E− vs. PVAT+E− L-NAME.
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Figure 2: Reduced eNOS expression and NO availability in abdominal vs. thoracic perivascular adipose tissue (PVAT). (A) eNOS protein expression in vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. Representative blots and Ponceau S staining were demonstrated at the upper panels of the figure and densitometric analysis is expressed as a fold change of THO expression at the bottom panel. (B) Top panels-Representative fluorographs of 4,5-diaminofluorescein diacetate (DAF-2) signal obtained in transverse sections of vessel walls and PVAT from THO and ABD aortic tissues in the absence (upper panel) and presence (lower panel) of L-NAME. Scale bar = 100 μm (20X objective). Bottom panel-Quantified NO availability, measured as DAF-2 fluorescence intensity in the endothelial layer and PVAT of THO and ABD aorta. (C) Concentration-response curves to phenylephrine in rat thoracic (left panel) and abdominal (right panel) aorta without (−) endothelium (E) and with (+) PVAT in the absence or presence of L-NAME. Data are expressed as the means ± SEM; the number of animals is indicated in the bars or in parenthesis. Student's t-test, P < 0.05: *ABD vs. THO PVAT; Two-way ANOVA, P < 0.05: & PVAT+E− vs. PVAT+E− L-NAME.

Mentions: There was a non-significant trend (p < 0.07) toward reduced eNOS protein expression in the abdominal when compared to the thoracic aorta (Figure 2A), whereas abdominal PVAT showed a 60% reduction in eNOS expression compared with thoracic PVAT (Figure 2A). In accordance with these data, NO availability evaluated based on DAF-2 fluorescence was not significantly altered in the endothelium of abdominal vs. thoracic aorta (p < 0.053), but abdominal PVAT showed a decrease in NO availability of 34% compared with thoracic PVAT (Figure 2B). L-NAME incubation significantly reduced NO bioavailability in both the endothelium and PVAT of abdominal and thoracic portions of aorta (Figure 2B).


Different Anti-Contractile Function and Nitric Oxide Production of Thoracic and Abdominal Perivascular Adipose Tissues.

Victorio JA, Fontes MT, Rossoni LV, Davel AP - Front Physiol (2016)

Reduced eNOS expression and NO availability in abdominal vs. thoracic perivascular adipose tissue (PVAT). (A) eNOS protein expression in vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. Representative blots and Ponceau S staining were demonstrated at the upper panels of the figure and densitometric analysis is expressed as a fold change of THO expression at the bottom panel. (B) Top panels-Representative fluorographs of 4,5-diaminofluorescein diacetate (DAF-2) signal obtained in transverse sections of vessel walls and PVAT from THO and ABD aortic tissues in the absence (upper panel) and presence (lower panel) of L-NAME. Scale bar = 100 μm (20X objective). Bottom panel-Quantified NO availability, measured as DAF-2 fluorescence intensity in the endothelial layer and PVAT of THO and ABD aorta. (C) Concentration-response curves to phenylephrine in rat thoracic (left panel) and abdominal (right panel) aorta without (−) endothelium (E) and with (+) PVAT in the absence or presence of L-NAME. Data are expressed as the means ± SEM; the number of animals is indicated in the bars or in parenthesis. Student's t-test, P < 0.05: *ABD vs. THO PVAT; Two-way ANOVA, P < 0.05: & PVAT+E− vs. PVAT+E− L-NAME.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940415&req=5

Figure 2: Reduced eNOS expression and NO availability in abdominal vs. thoracic perivascular adipose tissue (PVAT). (A) eNOS protein expression in vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. Representative blots and Ponceau S staining were demonstrated at the upper panels of the figure and densitometric analysis is expressed as a fold change of THO expression at the bottom panel. (B) Top panels-Representative fluorographs of 4,5-diaminofluorescein diacetate (DAF-2) signal obtained in transverse sections of vessel walls and PVAT from THO and ABD aortic tissues in the absence (upper panel) and presence (lower panel) of L-NAME. Scale bar = 100 μm (20X objective). Bottom panel-Quantified NO availability, measured as DAF-2 fluorescence intensity in the endothelial layer and PVAT of THO and ABD aorta. (C) Concentration-response curves to phenylephrine in rat thoracic (left panel) and abdominal (right panel) aorta without (−) endothelium (E) and with (+) PVAT in the absence or presence of L-NAME. Data are expressed as the means ± SEM; the number of animals is indicated in the bars or in parenthesis. Student's t-test, P < 0.05: *ABD vs. THO PVAT; Two-way ANOVA, P < 0.05: & PVAT+E− vs. PVAT+E− L-NAME.
Mentions: There was a non-significant trend (p < 0.07) toward reduced eNOS protein expression in the abdominal when compared to the thoracic aorta (Figure 2A), whereas abdominal PVAT showed a 60% reduction in eNOS expression compared with thoracic PVAT (Figure 2A). In accordance with these data, NO availability evaluated based on DAF-2 fluorescence was not significantly altered in the endothelium of abdominal vs. thoracic aorta (p < 0.053), but abdominal PVAT showed a decrease in NO availability of 34% compared with thoracic PVAT (Figure 2B). L-NAME incubation significantly reduced NO bioavailability in both the endothelium and PVAT of abdominal and thoracic portions of aorta (Figure 2B).

Bottom Line: PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta.However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT.In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas Campinas, Brazil.

ABSTRACT
Divergent phenotypes between the perivascular adipose tissue (PVAT) surrounding the abdominal and the thoracic aorta might be implicated in regional aortic differences, such as susceptibility to atherosclerosis. Although PVAT of the thoracic aorta exhibits anti-contractile function, the role of PVAT in the regulation of the vascular tone of the abdominal aorta is not well defined. In the present study, we compared the anti-contractile function, nitric oxide (NO) availability, and reactive oxygen species (ROS) formation in PVAT and vessel walls of abdominal and thoracic aorta. Abdominal and thoracic aortic tissue from male Wistar rats were used to perform functional and molecular experiments. PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta. Abdominal PVAT exhibited a reduction in endothelial NO synthase (eNOS) expression compared with thoracic PVAT, without differences in eNOS expression in the vessel walls. In agreement with this result, NO production evaluated in situ using 4,5-diaminofluorescein was less pronounced in abdominal compared with thoracic aortic PVAT, whereas no significant difference was observed for endothelial NO production. Moreover, NOS inhibition with L-NAME enhanced the phenylephrine-induced contraction in endothelial-denuded rings with PVAT from thoracic but not abdominal aorta. ROS formation and lipid peroxidation products evaluated through the quantification of hydroethidine fluorescence and 4-hydroxynonenal adducts, respectively, were similar between PVAT and vessel walls from the abdominal and thoracic aorta. Extracellular superoxide dismutase (SOD) expression was similar between the vessel walls and PVAT of the abdominal and thoracic aorta. However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT. In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta. Although relative SOD isoforms are different along the aorta, ROS formation, and lipid peroxidation seem to be similar. These findings highlight the specific regional roles of PVAT depots in the control of vascular function that can drive differences in susceptibility to vascular injury.

No MeSH data available.


Related in: MedlinePlus