High angiotensin II responsiveness is associated with decreased endothelium-dependent relaxation in human arteries.
BACKGROUND
Animal studies demonstrated an interaction between angiotensin II (Ang II) responsiveness and endothelium-dependent relaxation (EDR). However, this relation has not been well described in humans. Therefore, we investigated the relation between Ang II responsiveness and EDR in isolated human arteries.


METHODS
Segments of the internal mammary artery (IMA) were harvested from 89 patients undergoing coronary bypass surgery. Rings of these segments were exposed in organ bath experiments to metacholine (ME; 10 nmol/L-0.1 mmol/L) after precontraction with phenylephrine (PE; 10 micromol/L), and secondly to increasing concentrations of Ang II (0.1 nmol/L-1 micromol/L).


RESULTS
Patients with the highest contraction to Ang II showed the lowest ME relaxation (r=0.312; p=0.003). Angiotensin-converting enzyme (ACE)-inhibition significantly increased Ang II sensitivity (p=0.03). This increase was accompanied by a tendency toward decreased EDR (p=0.07). The inverse relation between Ang responsiveness and endothelium-dependent relaxation could not be explained by an increased tissue or serum ACE-inhibition in patients with a higher endothelium-dependent relaxation.


CONCLUSIONS
High Ang II responsiveness inversely correlates to EDR in IMA's of patients with established coronary artery disease. Short-term treatment with an ACE-inhibitor increased the response to Ang II, but had an adverse effect on EDR.
Voors
Adriaan A
AA
Department of Cardiology, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands. a.a.voors@thorax.umcg.nl
van Geel
Peter Paul
PP
Buikema
Hendrik
H
Oosterga
Margreeth
M
van Veldhuisen
Dirk J
DJ
van Gilst
Wiek H
WH
D000804:Angiotensin II / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000503:physiopathology; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D045462:Endothelium-Dependent Relaxing Factors; D016210:Methacholine Chloride; D000804:Angiotensin II