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Impaired Coronary Endothelial Vasorelaxation in a Preclinical Model of Peripheral Arterial Insufficiency.

Arce-Esquivel AA, Bunker AK, Simmons GH, Yang HT, Laughlin MH, Terjung RL - J Heart Cardiol (2015)

Bottom Line: Vasorelaxation to ADP was reduced in LADs from Occl-Sed and Occl-Ex pigs (P<0.001) as compared to Non-Occl-Con pigs; however, Occl-Ex pigs exhibited partial recovery (P<0.001) intermediate to the other two groups.In addition, SNP, PE, Ang II, and ET-1 responses were not significantly different among the groups.Our results indicate that 'simple' occlusion of the femoral arteries induces vascular dysfunction in conduit vessels distinct from the affected hindlimbs, as evident in blunted coronary vasorelaxation responses to ADP and BK.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri ; Department of Health and Kinesiology, The University of Texas at Tyler, Tyler, Texas.

ABSTRACT

The present study was designed to determine whether adult swine with peripheral artery insufficiency (PAI) would exhibit vascular dysfunction in vessels distinct from the affected distal limbs, the coronary conduit arteries. Moreover, we sought to evaluate the effect of exercise training on coronary vasomotor function in PAI. Eighteen female healthy young Yucatan miniature swine were randomly assigned to either occluded exercise trained (Occl-Ex, n=7), or occluded-sedentary (Occl-Sed, n=5), or non-occluded, non-exercised control (Non-Occl-Con, n=6) groups. Occl-Ex pigs were progressively trained by running on a treadmill (5days/week, 12 weeks). The left descending artery (LAD) and left circumflex (LCX) coronary arteries were harvested. Vasorelaxation to adenosine diphosphate (ADP), bradykinin (BK), and sodium nitro-prusside (SNP) were assessed in LAD's; while constrictor responses to phenylephrine (PE), angiotensin II (Ang II), and endothelin-1 (ET-1) were assessed in LCX's. Vasorelaxation to ADP was reduced in LADs from Occl-Sed and Occl-Ex pigs (P<0.001) as compared to Non-Occl-Con pigs; however, Occl-Ex pigs exhibited partial recovery (P<0.001) intermediate to the other two groups. BK induced relaxation was reduced in LADs from Occl-Ex and Occl-Sed pigs (P<0.001), compared to Non-Occl-Con, and exercise modestly increased responses to BK (P<0.05). In addition, SNP, PE, Ang II, and ET-1 responses were not significantly different among the groups. Our results indicate that 'simple' occlusion of the femoral arteries induces vascular dysfunction in conduit vessels distinct from the affected hindlimbs, as evident in blunted coronary vasorelaxation responses to ADP and BK. These findings imply that PAI, even in the absence of frank atherogenic vascular disease, contributes to vascular dysfunction in the coronary arteries that could exacerbate disease outcome in patients with peripheral artery disease. Further, regular daily physical activity partially recovered the deficit observed in the coronary arteries.

No MeSH data available.


Related in: MedlinePlus

Concentration-response curves for bradykinin (BK)-induced relaxation of isolated left descending coronary artery rings from non-occluded control (Non-Occl-Con, n=6); occluded exercise trained (Occl-Ex, n=7), and occluded sedentary (Occl-Sed, n=5) pigs. Data were obtained for Intact vessels (panel A); in the presence of L-NAME (panel B); in the presence of Indo (panel C); in the presence of both, L-NAME + Indo (panel D); in the presence of L-NAME + Indo + 30mM KCl (panel E); and denuded vessels (panel F). Values are means ± SE.* Non-Occl-Con different from both Occl-Sed and Occl-Ex (P<0.001); β (P<0.05);** Occl-Ex greater than Occl-Sed (P<0.001);†L-Name decreased values in all groups;ΩIndo increased values in Occl-Sed and Occl-Ex groups (P<0.001);∞L-NAME + Indo reduced values of the Non-Occl-Con group (P<0.001), but not in the Occl-Sed or Occl-Ex groups, and eliminated the modest training improvement observed at the intermediate doses (cf., Figure 1 panel A);ΔAddition of L-NAME + Indo reduced values in all groups (P<0.001).
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Figure 1: Concentration-response curves for bradykinin (BK)-induced relaxation of isolated left descending coronary artery rings from non-occluded control (Non-Occl-Con, n=6); occluded exercise trained (Occl-Ex, n=7), and occluded sedentary (Occl-Sed, n=5) pigs. Data were obtained for Intact vessels (panel A); in the presence of L-NAME (panel B); in the presence of Indo (panel C); in the presence of both, L-NAME + Indo (panel D); in the presence of L-NAME + Indo + 30mM KCl (panel E); and denuded vessels (panel F). Values are means ± SE.* Non-Occl-Con different from both Occl-Sed and Occl-Ex (P<0.001); β (P<0.05);** Occl-Ex greater than Occl-Sed (P<0.001);†L-Name decreased values in all groups;ΩIndo increased values in Occl-Sed and Occl-Ex groups (P<0.001);∞L-NAME + Indo reduced values of the Non-Occl-Con group (P<0.001), but not in the Occl-Sed or Occl-Ex groups, and eliminated the modest training improvement observed at the intermediate doses (cf., Figure 1 panel A);ΔAddition of L-NAME + Indo reduced values in all groups (P<0.001).

Mentions: BK-induced concentration-dependent relaxation in LAD rings was less (P<0.001) in intact rings from both Occl-Ex and Occl-Sed pigs than the Non-Occl-Con pigs (Fig. 1A). This reduced sensitivity to BK in the femoral occluded groups is also indicated by greater EC50 (P<0.05) by approximately a log-dose (Table 2). The Occl-Ex group exhibited a modest improvement in vasodilatation (P<0.001) in a dose-dependent manner, compared to the Occl-Sed group. BK-induced relaxation was partially inhibited by the addition of L-NAME in all three groups (P<0.001) (Fig. 1B); while the relative relationship among dose-response curves of the groups was not changed, the modest improvement at the two doses in the Occl-Ex group was eliminated suggesting the importance of NO in the Occl-Ex group. Addition of Indo to the baths increased relaxation in both Occl-Ex and Occl-Sed groups (P<0.001), suggesting the presence of a prostanoid constrictor in the occluded vessels (Fig. 1C). However, BK-induced relaxation of the Non-Occl-Con rings was more sensitive (P<0.001), indicating the presence of a COX-sensitive vasoconstrictor even in the absence of occlusion. With the combination of inhibitors, L-Name and Indo, BK-induced relaxation was reduced in all three groups (P<0.001), with a marked reduction in the Non-Occl-Con group such that the values were now below those of the Occl-Sed and Occl-Ex groups (P<0.001; Fig. 1D). BK-induced relaxation was almost completely inhibited by L-NAME + Indo + KCl in all three groups (Fig. 1E). Finally, when the endothelium was mechanically removed, BK-induced vasorelaxation was completely abolished in all three groups (Fig. 1F).


Impaired Coronary Endothelial Vasorelaxation in a Preclinical Model of Peripheral Arterial Insufficiency.

Arce-Esquivel AA, Bunker AK, Simmons GH, Yang HT, Laughlin MH, Terjung RL - J Heart Cardiol (2015)

Concentration-response curves for bradykinin (BK)-induced relaxation of isolated left descending coronary artery rings from non-occluded control (Non-Occl-Con, n=6); occluded exercise trained (Occl-Ex, n=7), and occluded sedentary (Occl-Sed, n=5) pigs. Data were obtained for Intact vessels (panel A); in the presence of L-NAME (panel B); in the presence of Indo (panel C); in the presence of both, L-NAME + Indo (panel D); in the presence of L-NAME + Indo + 30mM KCl (panel E); and denuded vessels (panel F). Values are means ± SE.* Non-Occl-Con different from both Occl-Sed and Occl-Ex (P<0.001); β (P<0.05);** Occl-Ex greater than Occl-Sed (P<0.001);†L-Name decreased values in all groups;ΩIndo increased values in Occl-Sed and Occl-Ex groups (P<0.001);∞L-NAME + Indo reduced values of the Non-Occl-Con group (P<0.001), but not in the Occl-Sed or Occl-Ex groups, and eliminated the modest training improvement observed at the intermediate doses (cf., Figure 1 panel A);ΔAddition of L-NAME + Indo reduced values in all groups (P<0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696773&req=5

Figure 1: Concentration-response curves for bradykinin (BK)-induced relaxation of isolated left descending coronary artery rings from non-occluded control (Non-Occl-Con, n=6); occluded exercise trained (Occl-Ex, n=7), and occluded sedentary (Occl-Sed, n=5) pigs. Data were obtained for Intact vessels (panel A); in the presence of L-NAME (panel B); in the presence of Indo (panel C); in the presence of both, L-NAME + Indo (panel D); in the presence of L-NAME + Indo + 30mM KCl (panel E); and denuded vessels (panel F). Values are means ± SE.* Non-Occl-Con different from both Occl-Sed and Occl-Ex (P<0.001); β (P<0.05);** Occl-Ex greater than Occl-Sed (P<0.001);†L-Name decreased values in all groups;ΩIndo increased values in Occl-Sed and Occl-Ex groups (P<0.001);∞L-NAME + Indo reduced values of the Non-Occl-Con group (P<0.001), but not in the Occl-Sed or Occl-Ex groups, and eliminated the modest training improvement observed at the intermediate doses (cf., Figure 1 panel A);ΔAddition of L-NAME + Indo reduced values in all groups (P<0.001).
Mentions: BK-induced concentration-dependent relaxation in LAD rings was less (P<0.001) in intact rings from both Occl-Ex and Occl-Sed pigs than the Non-Occl-Con pigs (Fig. 1A). This reduced sensitivity to BK in the femoral occluded groups is also indicated by greater EC50 (P<0.05) by approximately a log-dose (Table 2). The Occl-Ex group exhibited a modest improvement in vasodilatation (P<0.001) in a dose-dependent manner, compared to the Occl-Sed group. BK-induced relaxation was partially inhibited by the addition of L-NAME in all three groups (P<0.001) (Fig. 1B); while the relative relationship among dose-response curves of the groups was not changed, the modest improvement at the two doses in the Occl-Ex group was eliminated suggesting the importance of NO in the Occl-Ex group. Addition of Indo to the baths increased relaxation in both Occl-Ex and Occl-Sed groups (P<0.001), suggesting the presence of a prostanoid constrictor in the occluded vessels (Fig. 1C). However, BK-induced relaxation of the Non-Occl-Con rings was more sensitive (P<0.001), indicating the presence of a COX-sensitive vasoconstrictor even in the absence of occlusion. With the combination of inhibitors, L-Name and Indo, BK-induced relaxation was reduced in all three groups (P<0.001), with a marked reduction in the Non-Occl-Con group such that the values were now below those of the Occl-Sed and Occl-Ex groups (P<0.001; Fig. 1D). BK-induced relaxation was almost completely inhibited by L-NAME + Indo + KCl in all three groups (Fig. 1E). Finally, when the endothelium was mechanically removed, BK-induced vasorelaxation was completely abolished in all three groups (Fig. 1F).

Bottom Line: Vasorelaxation to ADP was reduced in LADs from Occl-Sed and Occl-Ex pigs (P<0.001) as compared to Non-Occl-Con pigs; however, Occl-Ex pigs exhibited partial recovery (P<0.001) intermediate to the other two groups.In addition, SNP, PE, Ang II, and ET-1 responses were not significantly different among the groups.Our results indicate that 'simple' occlusion of the femoral arteries induces vascular dysfunction in conduit vessels distinct from the affected hindlimbs, as evident in blunted coronary vasorelaxation responses to ADP and BK.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri ; Department of Health and Kinesiology, The University of Texas at Tyler, Tyler, Texas.

ABSTRACT

The present study was designed to determine whether adult swine with peripheral artery insufficiency (PAI) would exhibit vascular dysfunction in vessels distinct from the affected distal limbs, the coronary conduit arteries. Moreover, we sought to evaluate the effect of exercise training on coronary vasomotor function in PAI. Eighteen female healthy young Yucatan miniature swine were randomly assigned to either occluded exercise trained (Occl-Ex, n=7), or occluded-sedentary (Occl-Sed, n=5), or non-occluded, non-exercised control (Non-Occl-Con, n=6) groups. Occl-Ex pigs were progressively trained by running on a treadmill (5days/week, 12 weeks). The left descending artery (LAD) and left circumflex (LCX) coronary arteries were harvested. Vasorelaxation to adenosine diphosphate (ADP), bradykinin (BK), and sodium nitro-prusside (SNP) were assessed in LAD's; while constrictor responses to phenylephrine (PE), angiotensin II (Ang II), and endothelin-1 (ET-1) were assessed in LCX's. Vasorelaxation to ADP was reduced in LADs from Occl-Sed and Occl-Ex pigs (P<0.001) as compared to Non-Occl-Con pigs; however, Occl-Ex pigs exhibited partial recovery (P<0.001) intermediate to the other two groups. BK induced relaxation was reduced in LADs from Occl-Ex and Occl-Sed pigs (P<0.001), compared to Non-Occl-Con, and exercise modestly increased responses to BK (P<0.05). In addition, SNP, PE, Ang II, and ET-1 responses were not significantly different among the groups. Our results indicate that 'simple' occlusion of the femoral arteries induces vascular dysfunction in conduit vessels distinct from the affected hindlimbs, as evident in blunted coronary vasorelaxation responses to ADP and BK. These findings imply that PAI, even in the absence of frank atherogenic vascular disease, contributes to vascular dysfunction in the coronary arteries that could exacerbate disease outcome in patients with peripheral artery disease. Further, regular daily physical activity partially recovered the deficit observed in the coronary arteries.

No MeSH data available.


Related in: MedlinePlus