Vasoconstriction to endogenous endothelin-1 is impaired in patients with type II diabetes mellitus.
Endothelin-1 has potent vasoconstrictor and vasopressor actions contributing to basal vascular tone and maintenance of blood pressure acting predominantly through endothelin-A receptors. Endothelin antagonists may be of value in the treatment of hypertension and heart failure. However, the role of endothelin-1 in the regulation of vascular tone and the potential benefits of endothelin antagonists in non-insulin-dependent diabetes mellitus (Type II diabetes) are less clear. Vasoconstriction to exogenous endothelin-1 is impaired in Type II diabetes. The purpose of this study was to determine whether vasoconstriction to endogenous endothelin-1 acting through the endothelin-A receptor is impaired in Type II diabetes. In ten patients with Type II diabetes and nine controls the endothelin-A receptor antagonist BQ123 was infused intra-arterially at 100 nmol/min for 60 min followed by normal saline for 30 min. Forearm blood flow was measured using venous occlusion plethysmography. Control subjects showed gradual onset of vasodilation in response to BQ123 (P < 0.001). Diabetic subjects, however, showed no significant response (P > 0.05). There was a significant difference between the diabetic and control groups (P < 0.05). Blockade of the endothelin-A receptor is associated with impaired vasodilation in Type II diabetes indicating vasoconstriction to endogenous endothelin-1 mediated by the endothelin-A receptor is impaired.
McAuley
D F
DF
Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Northern Ireland, UK.
Nugent
A G
AG
McGurk
C
C
Maguire
S
S
Hayes
J R
JR
Johnston
G D
GD
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)