Microvascular versus macrovascular dysfunction in type 2 diabetes

Differences in contractile responses to endothelin-1

Kamakshi Sachidanandam, Alex Harris, Jimmie Hutchinson, Adviye Ergul

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1016-1021
Number of pages6
JournalExperimental Biology and Medicine
Volume231
Issue number6
StatePublished - Jun 1 2006

Fingerprint

Endothelin-1
Medical problems
Basilar Artery
Type 2 Diabetes Mellitus
Blood Vessels
Nitric Oxide Synthase
Mesenteric Arteries
Endothelins
Vasoconstrictor Agents
Serotonin
Rats
Rat control
Vasodilation
Hyperglycemia
Blood pressure
Acetylcholine
Arginine
Cardiovascular Diseases
Blood Pressure
Incidence

Keywords

  • Endothelin-1
  • Goto-kakizaki
  • Type 2 diabetes
  • Vascular dysfunction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Microvascular versus macrovascular dysfunction in type 2 diabetes : Differences in contractile responses to endothelin-1. / Sachidanandam, Kamakshi; Harris, Alex; Hutchinson, Jimmie; Ergul, Adviye.

In: Experimental Biology and Medicine, Vol. 231, No. 6, 01.06.2006, p. 1016-1021.

Research output: Contribution to journalArticle

Sachidanandam, Kamakshi ; Harris, Alex ; Hutchinson, Jimmie ; Ergul, Adviye. / Microvascular versus macrovascular dysfunction in type 2 diabetes : Differences in contractile responses to endothelin-1. In: Experimental Biology and Medicine. 2006 ; Vol. 231, No. 6. pp. 1016-1021.
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