TY - JOUR
T1 - Microvascular versus macrovascular dysfunction in type 2 diabetes
T2 - Differences in contractile responses to endothelin-1
AU - Sachidanandam, Kamakshi
AU - Harris, Alex
AU - Hutchinson, Jimmie
AU - Ergul, Adviye
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (HL076236-01), an American Diabetes Association Research Award, and a Philip Morris Research Award to A.E.
PY - 2006/6
Y1 - 2006/6
N2 - Vascular dysfunction characterized by a hyperreactivity to vasoconstrictors and/or impaired vascular relaxation contributes to increased incidence of cardiovascular disease in diabetes. Endothelin (ET)-1, a potent vasoconstrictor, is chronically elevated in diabetes. However, the role of ET-1 in resistance versus larger vessel function in mild diabetes remains unknown. Accordingly, this study investigated vascular function of third-order mesenteric arteries and basilar arteries in control Wistar and Goto-Kakizaki (GK) rats, a model of mild Type 2 diabetes. Six weeks after the onset of diabetes, contractile responses to 0.1-100 nM ET-1 and relaxation responses to 1 nM-10 μM acetylcholine (ACh) in vessels preconstricted (baseline + 60%) with serotonin (5-HT) were assessed by myograph studies in the presence or absence of a nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine (L-NNA). Maximum contractile response to ET-1 was augmented in mesenteric vessels (155 ± 18% in GK vs. 81 ± 6% in control; n = 5-7) but not in the basilar artery (134 ± 29% in GK vs. 107 ± 17% in control; n = 4 per group). However, vascular relaxation was impaired in the basilar arteries (22 ± 4% in GK vs. 53 ± 7% in control; n = 4 per group) but not in mesenteric arteries of GK rats. Inhibition of NOS decreased the relaxation response of basilar arteries to 15 ± 8% and 42 ± 5% in GK and control rats, respectively; whereas, in resistance vessels, corresponding values were 56 ± 7% and 89 ± 3% (vs. 109 ± 2% and 112 ± 3% without NOS blockade), indicating the involvement of different vasorelaxation-promoting pathways in these vascular beds. These findings provide evidence that the ET system is activated even under mild hyperglycemia and that it contributes to the hyperreactivity of resistance vessels, therefore, the ET system may play an important role in elevated blood pressure in Type 2 diabetes.
AB - Vascular dysfunction characterized by a hyperreactivity to vasoconstrictors and/or impaired vascular relaxation contributes to increased incidence of cardiovascular disease in diabetes. Endothelin (ET)-1, a potent vasoconstrictor, is chronically elevated in diabetes. However, the role of ET-1 in resistance versus larger vessel function in mild diabetes remains unknown. Accordingly, this study investigated vascular function of third-order mesenteric arteries and basilar arteries in control Wistar and Goto-Kakizaki (GK) rats, a model of mild Type 2 diabetes. Six weeks after the onset of diabetes, contractile responses to 0.1-100 nM ET-1 and relaxation responses to 1 nM-10 μM acetylcholine (ACh) in vessels preconstricted (baseline + 60%) with serotonin (5-HT) were assessed by myograph studies in the presence or absence of a nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine (L-NNA). Maximum contractile response to ET-1 was augmented in mesenteric vessels (155 ± 18% in GK vs. 81 ± 6% in control; n = 5-7) but not in the basilar artery (134 ± 29% in GK vs. 107 ± 17% in control; n = 4 per group). However, vascular relaxation was impaired in the basilar arteries (22 ± 4% in GK vs. 53 ± 7% in control; n = 4 per group) but not in mesenteric arteries of GK rats. Inhibition of NOS decreased the relaxation response of basilar arteries to 15 ± 8% and 42 ± 5% in GK and control rats, respectively; whereas, in resistance vessels, corresponding values were 56 ± 7% and 89 ± 3% (vs. 109 ± 2% and 112 ± 3% without NOS blockade), indicating the involvement of different vasorelaxation-promoting pathways in these vascular beds. These findings provide evidence that the ET system is activated even under mild hyperglycemia and that it contributes to the hyperreactivity of resistance vessels, therefore, the ET system may play an important role in elevated blood pressure in Type 2 diabetes.
KW - Endothelin-1
KW - Goto-kakizaki
KW - Type 2 diabetes
KW - Vascular dysfunction
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M3 - Article
C2 - 16741041
AN - SCOPUS:33744906508
SN - 1535-3702
VL - 231
SP - 1016
EP - 1021
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 6
ER -