Background: We have shown that treatment of hypertension with ACE inhibitors (ACE-I) enhances relaxation to acetylcholine in human internal thoracic artery (ITA) above this in nonhypertensive patients receiving no ACE-I. Present study assesses the endothelium-dependent responses mediated by neither NO nor prostacyclin in human ITA.
Methods: We compared isolated ITA rings from hypertensive patients treated with ACE-I (ACE-I group) with those from normotensive patients on no ACE-I (control group). Relaxation to acetylcholine was assessed before and after inhibition of NO synthase and cyclooxygenase with L-NMMA and indomethacin, respectively.
Results: The maximal relaxation in ACE-I group was 79+/-3.3% and was depressed by incubation with L-NMMA and indomethacin to 41+/-2.7% (p<0.001); pD(2)=7.7+/-0.1 vs. 7.4+/-0.8 (p=0.265). The maximal relaxation to acetylcholine was lower in the control group: 65+/-3.3% (p=0.01); pD(2)=7.5+/-0.1 (p=0.07). Incubation with L-NMMA and indomethacin produced contraction to acetylcholine with a maximum of 43+/-7% (p<0.001); pD(2)=5.3+/-0.3 (p<0.001). The area under the concentration-response curve for acetylcholine-induced relaxation in ACE-I group equaled [arbitrary units] 596+/-71 and after incubation with L-NMMA and indomethacin 281+/-40 (p=0.002). Estimated LNMMA- and indomethacin-resistant relaxation, absent in control group, accounted for 47+/-4% of relaxation to acetylcholine in ACE-I group. Estimated NO- and prostacyclin-mediated relaxation was higher in control group than ACE-I group: 628+/-74 vs. 315+/-47 (p=0.009).
Conclusions: The results suggest that therapy with ACE-I improves endothelial function of hypertensive patients mainly by enhancing the endothelium-derived hyperpolarizing factor (EDHF) (and not NO)-mediated responses. It seems that it reveals measurable non-NO- non-PGI-mediated endothelium-dependent relaxation otherwise absent in conduit arteries.