Angiotensin-converting enzyme inhibitors reveal non-NO-, non-prostacycline-mediated endothelium-dependent relaxation in internal thoracic artery of hypertensive patients.
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.
Deja
Marek A
MA
2nd Department of Cardiac Surgery, Medical University of Silesia, Ul. Ziołowa 47, 40-635 Katowice, Poland. narizol@slam.katowice.pl
Gołba
Krzysztof S
KS
Widenka
Kazimierz
K
Mrozek
Roman
R
Biernat
Jolanta
J
Kolowca
Maciej
M
Malinowski
Marcin
M
Woś
Stanisław
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D011464:Epoprostenol; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide; D013895:Thoracic Arteries / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D011464:Epoprostenol