Augmented response of endothelin-A and endothelin-B receptor stimulation in coronary arteries of hypertensive hearts.
To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is altered in coronary vessels of hypertensive hearts and the role of ETA and ETB receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in coronary vessels was measured with or without ETA and ETB receptor antagonists. In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent increases of CPR in both normotensive and SHR rat hearts. However, the responses were significantly greater in SHR than those of WKY. Pretreatment with the ETA antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET-1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR than in WKY after FR139317 or BQ788 infusion. These findings suggest that the augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both ETA and ETB receptors. These changes may contribute to the impaired coronary circulation in hypertension.
Miki
S
S
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Takeda
K
K
Kiyama
M
M
Hatta
T
T
Morimoto
S
S
Kawa
T
T
Itoh
H
H
Nakata
T
T
Sasaki
S
S
Nakagawa
M
M
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists*; D014661:Vasoconstriction / Q000187:drug effects*
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C079574:FR 139317; C086539:BQ 788