Effects of cyclooxygenase inhibition on endothelial function in hypertensive patients treated with angiotensin-converting enzyme inhibitors.
BACKGROUND
Cyclooxygenase inhibition restores endothelium-dependent vasodilatation in hypertension, but it is unknown whether it restores endothelial function in hypertensive patients treated with angiotensin-converting enzyme (ACE) inhibitors.


OBJECTIVE
The purpose of the present study was to evaluate the effects of cyclooxygenase inhibition on endothelial function in hypertensive patients treated with ACE inhibitors.


METHODS
Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent glyceryl trinitrate-induced dilatation were investigated in 10 patients treated with enalapril (ACE group), 11 patients treated with manidipine and metoprolol (non-ACE group), and 12 normotensive control subjects. After administration of 1000 mg of aspirin, FMD was investigated once again. Plasma cyclic guanosine monophosphate (cGMP) and eicosanoids were also measured during reactive hyperemia before and after aspirin administration.


RESULTS
Flow-mediated dilatation was more impaired in the non-ACE group than in the ACE group (8.3 +/- 3.8%, 5.7 +/- 1.7%, respectively, p<0.04). Glyceryl trinitrate-induced dilatation was similar in the ACE group, the non-ACE group, and in the control subjects. In the ACE group, FMD was reduced after administration of aspirin (5.3 +/- 4.2%, p<0.05). The percent change in FMD after administration of aspirin correlated significantly with percent change in cGMP (r=0.77, p<0.03; y-intercept, -62.1%, p<0.01). After aspirin administration, levels of thromboxane B2 and 6-keto-prostaglandin(1alpha) were significantly decreased compared with those before aspirin administration in all groups.


CONCLUSIONS
Cyclooxygenase inhibition may reduce the beneficial effect on endothelium-dependent vasodilatation induced by ACE inhibitors. The results suggested that prostacyclin in addition to nitric oxide plays a significant role in the restoration of endothelial function in hypertensive patients treated with ACE inhibitors.
Department of Cardiovascular Medicine, Okayama University Medical School, Okayama, Japan. hyama@mx31.tiki.ne.jp
Hiroshi
H
Yamanari
Kazufumi
K
Nakamura
Mikio
M
Kakishita
Tohru
T
Ohe
D000286:Administration, Sublingual; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D001241:Aspirin; D016022:Case-Control Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage; D004656:Enalapril / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage; D008875:Middle Aged; D009578:Nitrobenzenes; D005996:Nitroglycerin; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D012039:Regional Blood Flow; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D004656:Enalapril; C054218:manidipine; D005996:Nitroglycerin; D008790:Metoprolol; D001241:Aspirin