title: Integrative control of coronary resistance vessel tone by endothelin and angiotensin II is altered in swine with a recent myocardial infarction.
abstract: Several studies have indicated an interaction between the renin-angiotensin (ANG II) system and endothelin (ET) in the regulation of vascular tone. Previously, we have shown that both ET and ANG II exert a vasoconstrictor influence on the coronary resistance vessels of awake normal swine. Here, we investigated whether the interaction between ANG II and ET exists in the control of coronary resistance vessel tone at rest and during exercise using single and combined blockade of angiotensin type 1 (AT(1)) and ET(A)/ET(B) receptors. Since both circulating ANG II and ET levels are increased after myocardial infarction (MI), we investigated if the interaction between these systems is altered after MI. In awake healthy swine, coronary vasodilation in response to ET(A)/ET(B) receptor blockade in the presence of AT(1) blockade was similar to vasodilation produced by ET(A)/ET(B) blockade under control conditions. In awake swine with a 2- to 3-wk-old MI, coronary vasodilator responses to individual AT(1) and ET(A)/ET(B) receptor blockade were virtually abolished, despite similar coronary arteriolar AT(1) and ET(A) receptor expression compared with normal swine. Unexpectedly, in the presence of AT(1) blockade (which had no effect on circulating ET levels), ET(A)/ET(B) receptor blockade elicited a coronary vasodilator response. These findings suggest that in normal healthy swine the two vasoconstrictor systems contribute to coronary resistance vessel control in a linear additive manner, i.e., with negligible cross-talk. In contrast, in the remodeled myocardium, cross-talk between ANG II and ET emerges, resulting in nonlinear redundant control of coronary resistance vessel tone.
authors.affiliation: Division of Experimental Cardiology, Thoraxcenter, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: de Beer
authors.forename: Oana
authors.initials: O
authors.lastname: Sorop
authors.forename: Daniël A
authors.initials: DA
authors.lastname: Pijnappels
authors.forename: Dick H
authors.initials: DH
authors.lastname: Dekkers
authors.forename: Frans
authors.initials: F
authors.lastname: Boomsma
authors.forename: Jos M J
authors.initials: JM
authors.lastname: Lamers
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: Daphne
authors.initials: D
authors.lastname: Merkus
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D006439:Hemodynamics; D000077405:Irbesartan; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism; D005082:Physical Exertion; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction; D014664:Vasodilation; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013777:Tetrazoles; D000804:Angiotensin II; C120582:tezosentan; D000077405:Irbesartan; D010100:Oxygen