Angiotensin II type 2 receptor vasoactivity in internal mammary arteries of patients with coronary artery disease.
BACKGROUND
Several animal studies suggested that the angiotensin II type 2 (AT2) receptor subtype mediates vasodilation, yet the results in human arteries are less well described and more inconsistent. Therefore, we evaluated the role of the AT2 receptor stimulation on the vasotonus of human internal mammary arteries.


METHODS
Internal mammary arteries were obtained from 50 patients undergoing coronary bypass surgery. The expression of angiotensin II type 1 (AT1) receptor and AT2 receptor mRNA was determined by using real-time polymerase chain reaction. In addition, angiotensin II and CGP42112A concentration-response curves (concentration range: 10(-10) M to 10(-6) M) were constructed in absence or presence of candesartan (10(-5) M) and/or the AT2 receptor-antagonist PD-123319 (10(-6) M) and/or the alpha receptor antagonist phentolamine.


RESULTS
Both AT1 and AT2 receptor protein and mRNA were detected, and higher AT2 receptor mRNA expression levels were associated with increased contractile response to angiotensin II. Angiotensin II caused vasoconstriction up to 41.1 +/- 6.5% of the maximal response to phenylephrine, and PD123319 significantly reduced this response (28.6 +/- 9.6%, P < 0.001). Candesartan completely blocked the angiotensin II-mediated response (1.4 +/- 3.1%, P < 0.001 versus control), and additional blockade of the AT2 receptor with PD123319 did not change this effect (1.8 +/- 5.1%). Phentolamine (10(-5) M) caused attenuation and rightward shift of the angiotensin II concentration response curves. The AT2 receptor agonist CGP42112A did not induce a significant response.


CONCLUSIONS
Although AT2 receptor mRNA is present in human internal mammary arteries, AT2 receptor stimulation does not mediate vasodilation in these arteries.
Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands. r.wal@antonius.net
R M A
RM
van de Wal
P
P
van der Harst
L J
LJ
Wagenaar
S
S
Wassmann
W J
WJ
Morshuis
G
G
Nickenig
H
H
Buikema
H W M
HW
Plokker
D J
DJ
van Veldhuisen
W H
WH
van Gilst
A A
AA
Voors
D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D003324:Coronary Artery Disease / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012977:Sodium Nitrite / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D010656:Phenylephrine; D012977:Sodium Nitrite; D000109:Acetylcholine; C081643:candesartan; D010646:Phentolamine