Biological role for the endothelin-A receptor in aortic cross-clamping.
The current study was undertaken to define a biological role for the endothelin-A receptor in a clinically relevant model of altered systemic and renal function produced by suprarenal aortic cross-clamping. This model is associated with profound systemic and renal vasoconstriction, acute renal failure, and a significant increase in circulating endothelin. Studies were performed in three groups of anesthetized mongrel dogs. Group 1 (n = 5) underwent aortic cross-clamping for 1 hour; group 2 (n = 5) underwent aortic cross-clamping for 1 hour in the presence of BQ-123, a specific antagonist of the endothelin-A receptor; group 3 (n = 4) received BQ-123 alone. The marked systemic and renal vasoconstriction associated with aortic cross-clamping in group 1 was markedly attenuated in group 2 in the presence of BQ-123. Unlike the vasoconstrictor response, BQ-123 did not attenuate the decrease in glomerular filtration rate associated with this model. Under unstimulated conditions in group 3, BQ-123 had no actions on systemic or renal hemodynamics. In conclusion, the current study demonstrates that the systemic and renal vasoconstriction associated with aortic cross-clamping are in part mediated through the interaction of endothelin and the endothelin-A receptor. This study demonstrates the functional importance of increased endogenous endothelin in the regulation of vascular tone in this pathophysiological state.
Stingo
A J
AJ
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905.
Clavell
A L
AL
Aarhus
L L
LL
Burnett
J C
JC
D000818:Animals; D001011:Aorta / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output; D004195:Disease Models, Animal; D004285:Dogs; D016232:Endothelins / Q000097:blood; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000502:physiology*
D016232:Endothelins; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)