Angiotensin-converting enzyme inhibitors reveal non-NO-, non-prostacycline-mediated endothelium-dependent relaxation in internal thoracic artery of hypertensive patients

Abstract

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.