Key result
Combined ET(A) and ET(B) receptor blockade evoked a 102% increase in forearm blood flow in atherosclerotic patients compared to no effect (-3%) in healthy controls (P<0.001).
Why the study?
Does intra-arterial infusion of selective ET receptor antagonists alter forearm blood flow differently in patients with atherosclerosis compared to healthy controls?
Does intra-arterial infusion of selective ET receptor antagonists alter forearm blood flow differently in patients with atherosclerosis compared to healthy controls?
Absolute Event Rate: 102% vs -3%
p-value: p=<0.001
Atherosclerotic patients exhibit enhanced ET-1-mediated vascular tone, partly due to increased ET(B)-mediated vasoconstriction, suggesting altered endothelin receptor function in atherosclerosis.
Suggests enhanced ET-1 tone via ET(B) receptors in atherosclerosis; hypothesis-generating and should not yet change practice.
Endothelin (ET)-1 causes vasoconstriction via ET(A) and ET(B) receptors located on vascular smooth muscle cells and vasodilatation via ET(B) receptors on endothelial cells. Studies in vitro indicate an upregulation of ET(B) receptors in atherosclerosis. The present study investigated the vascular effects evoked by endogenous ET-1 in atherosclerotic patients. Forearm blood flow (FBF) was measured with venous occlusion plethysmography in 10 patients with atherosclerosis and in 10 healthy control subjects during intra-arterial infusion of selective ET receptor antagonists. The ET(B) receptor antagonist BQ788 evoked a significant increase in FBF (31+/-13%) in the patients, whereas a 20+/-9% reduction was observed in the control subjects. The ET(A) receptor antagonist BQ123 combined with BQ788 evoked a marked increase in FBF (102+/-25%) in the patients compared with no effect in the control subjects (-3+/-9%, P<0.001 versus patients). The ET(A) receptor antagonist BQ123 increased FBF to a similar degree in patients (39+/-11%) as in control subjects (41+/-11%). The increase in FBF evoked by selective ET(A) receptor blockade was significantly (P<0.05) less than that evoked by combined ET(A)/ET(B) receptor blockade in the atherosclerotic patients. These observations suggest an enhanced ET-1-mediated vascular tone in atherosclerotic patients, which is at least partly due to increased ET(B)-mediated vasoconstriction.
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Böhm et al. (2002) studied Atherosclerosis (n=20). Intra-arterial infusion of selective ET receptor antagonists (BQ123 and BQ788) vs. Healthy control subjects was evaluated on Change in forearm blood flow (FBF) during combined ET(A) and ET(B) receptor blockade (p=<0.001). Combined ET(A) and ET(B) receptor blockade evoked a 102% increase in forearm blood flow in atherosclerotic patients compared to no effect (-3%) in healthy controls (P<0.001).
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