Microvascular versus macrovascular dysfunction in type 2 diabetes: differences in contractile responses to
Kamakshi Sachidanandam1, Alex Harris, Jimmie Hutchinson
1Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta 30912, USA.
Experimental Biology and Medicine (Maywood, N.J.)
|June 3, 2006
Summary
In mild diabetes, the endothelin (ET) system is activated, causing increased constriction in small mesenteric arteries but not large basilar arteries. This ET system activation contributes to vascular dysfunction and potentially elevated blood pressure in Type 2 diabetes.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Vascular Biology
Background:
- Vascular dysfunction, marked by altered responses to vasoconstrictors and impaired relaxation, is a key factor in cardiovascular disease development in diabetes.
- Endothelin (ET)-1, a potent vasoconstrictor, is known to be elevated in diabetic conditions.
- The specific impact of ET-1 on resistance versus larger vessels in early-stage diabetes remains unclear.
Purpose of the Study:
- To investigate the role of the endothelin (ET) system in vascular dysfunction in mild Type 2 diabetes.
- To compare the effects of ET-1 on mesenteric resistance arteries and basilar arteries in a model of mild diabetes.
- To assess the contribution of nitric oxide synthase (NOS) to vascular responses in these vessels.
Main Methods:
- Utilized myograph studies to assess vascular function in third-order mesenteric arteries and basilar arteries from control Wistar and Goto-Kakizaki (GK) rats (a model of mild Type 2 diabetes).
- Measured contractile responses to Endothelin (ET)-1 and relaxation responses to acetylcholine (ACh) after preconstriction with serotonin (5-HT).
- Evaluated the role of nitric oxide synthase (NOS) by using the inhibitor N-nitro-L-arginine (L-NNA).
Main Results:
- Maximum contractile response to ET-1 was significantly augmented in mesenteric arteries of GK rats compared to controls, but not in basilar arteries.
- Vascular relaxation to acetylcholine was impaired in basilar arteries of GK rats but not in mesenteric arteries.
- NOS inhibition differentially affected relaxation in basilar arteries and mesenteric arteries, indicating distinct vasorelaxation pathways.
Conclusions:
- The endothelin (ET) system is activated even in mild hyperglycemia, contributing to hyperreactivity in resistance vessels.
- These findings suggest the ET system plays a significant role in the elevated blood pressure observed in Type 2 diabetes.
- Differential vascular responses highlight the complexity of vascular dysfunction in diabetes across different vessel types.
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