Crosstalk between endothelin and nitric oxide in the control of vascular tone.
Several lines of evidence indicate that nitric oxide (NO) impairs endothelin (ET) production/action in vitro. Acute pressor responses caused by the blockade of NO formation with arginine analogues in vivo are blunted by selective ET(A) or dual ET(A)/ET(B) receptor blockade whereas blockade of NO formation magnifies ET-induced constriction of various vascular territories. Given that ET receptor blockade has normally limited effects on mean arterial pressure, the reversal of pressor responses caused by the blockade of NO formation with ET receptor blockade most likely reflects a significant crosstalk between NO and ET. Suppression of NO formation also leads to significant increases in ET production caused by agents targeting the endothelium, such as acetylcholine and thrombin. In addition, the inhibitory effect of shear stress on endothelial cells ET production also involves NO as an intermediate.Paradoxically, chronic exposure to organic nitrates which causes nitrate tolerance leads to an augmented vascular ET content. An increased angiotensin II (AII) production is apparently pivotal in this process. This article reviews observations pointing to the importance of NO/ET interactions as a fundamental and common regulatory mechanism shared across species. As a consequence of this crosstalk between NO and ET, experimental strategies designed to assess endothelial NO-dependent activity by the blockade of NO formation may be mitigated by magnified ET-dependent influences.
Lavallée
M
M
Department of Physiology, Faculty of Medicine, Université de Montréal, and Institut de Cardiologie de Montréal, Montréal, Québec, Canada. lavallem@icm.umontreal.ca
Takamura
M
M
Parent
R
R
Thorin
E
E
D000818:Animals; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D017466:Receptors, Endothelin / Q000502:physiology; D013045:Species Specificity; D014655:Vascular Resistance / Q000502:physiology*
D016232:Endothelins; D017466:Receptors, Endothelin; D009569:Nitric Oxide