Angiotensin II type 2 receptor-mediated vasodilation in human coronary microarteries.
BACKGROUND
Angiotensin (Ang) II type 2 (AT2) receptor stimulation results in coronary vasodilation in the rat heart. In contrast, AT2 receptor-mediated vasodilation could not be observed in large human coronary arteries. We studied Ang II-induced vasodilation of human coronary microarteries (HCMAs).


RESULTS
HCMAs (diameter, 160 to 500 microm) were obtained from 49 heart valve donors (age, 3 to 65 years). Ang II constricted HCMAs, mounted in Mulvany myographs, in a concentration-dependent manner (pEC50, 8.6+/-0.2; maximal effect [E(max)], 79+/-13% of the contraction to 100 mmol/L K+). The Ang II type 1 receptor antagonist irbesartan prevented this vasoconstriction, whereas the AT2 receptor antagonist PD123319 increased E(max) to 97+/-14% (P<0.05). The increase in E(max) was larger in older donors (correlation DeltaE(max) versus age, r=0.47, P<0.05). The PD123319-induced potentiation was not observed in the presence of the NO synthase inhibitor L-NAME, the bradykinin type 2 (B2) receptor antagonist Hoe140, or after removal of the endothelium. Ang II relaxed U46619-preconstricted HCMAs in the presence of irbesartan by maximally 49+/-16%, and PD123319 prevented this relaxation. Finally, radioligand binding studies and reverse transcription-polymerase chain reaction confirmed the expression of AT2 receptors in HCMAs.


CONCLUSIONS
AT2 receptor-mediated vasodilation in the human heart appears to be limited to coronary microarteries and is mediated by B2 receptors and NO. Most likely, AT2 receptors are located on endothelial cells, and their contribution increases with age.
Batenburg
Wendy W
WW
Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
Garrelds
Ingrid M
IM
Bernasconi
Catherine Chapuis
CC
Juillerat-Jeanneret
Lucienne
L
van Kats
Jorge P
JP
Saxena
Pramod R
PR
Danser
A H Jan
AH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers; D001713:Biphenyl Compounds / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D000077405:Irbesartan; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D057912:Angiotensin II Type 2 Receptor Blockers; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D009569:Nitric Oxide; D006152:Cyclic GMP; D000077405:Irbesartan; D019331:NG-Nitroarginine Methyl Ester