Enhanced vasoconstrictor response to endothelin-B-receptor stimulation in patients with atherosclerosis

The vascular responses to endothelin-1 [ET-1; nonselective endothelin-A and -B (ET(A) and ET(B) agonist)] and sarafotoxin 6c (S6c; ET(B) agonist) were investigated in patients with atherosclerosis. ET-1 and S6c (3, 10 and 30 pmol/min) were infused into the brachial artery while forearm blood flow (FBF) was measured by venous occlusion plethysmography in seven male patients with atherosclerosis and six age-matched healthy male controls. S6c evoked an initial increase followed by a dose-dependent reduction in FBF. The initial dilator component did not differ between the two groups. The vasoconstrictor component of the two lower doses of S6c was significantly larger in the atherosclerotic patients than in controls. The reduction in FBF induced by 3 and 10 pmol/min S6c was 18 +/- 2% and 27 +/- 6% in the control group compared to 29 +/- 3% (p < 0.02) and 42 +/- 2% (p < 0.05) in patients with atherosclerosis. The vasoconstrictor response to S6c correlated with low-density lipoprotein (LDL) cholesterol levels (r = 0.47, p < 0.05). The vasoconstrictor response to ET-1 was similar in the two groups. It is concluded that the forearm vasoconstrictor response to S6c but not that to ET-1 is enhanced in patients with atherosclerosis as compared with healthy controls. This finding suggests an upregulation of vascular smooth muscle ET(B)-receptors in atherosclerosis.