Selected contribution: effects of ischemia-reperfusion on vascular contractility and alpha(1)-adrenergic-receptor signaling in the rat tail artery.
To determine the effects of ischemia-reperfusion (I/R) on alpha(1)-adrenergic-receptor (alpha(1)-AR) functions, alpha(1)-AR-mediated contraction, inositol phosphate (IP) accumulation, and alpha(1)-AR-G protein coupling were examined in the tail arteries of anesthetized rats after 60 min of ischemia and 60 min of reperfusion. The contractile response to norepinephrine (NE) was significantly increased after I/R, whereas the contractile response to KCl remained unchanged. This was accompanied by a 69% increase in NE-stimulated IP accumulation. Furthermore, receptor-stimulated coupling of alpha(1a)-AR to G alpha(q/11) proteins was increased, whereas the coupling of alpha(1b)-AR or alpha(1d)-AR to their G proteins was not altered by I/R. These changes in vascular alpha(1)-AR function occurred without concurrent alteration in expression levels of membrane alpha(1)-AR subtypes or in the associated G proteins. These data demonstrate that I/R increases alpha(1a)-AR-G(q/11) protein coupling and alpha(1)-AR-stimulated IP accumulation in the tail artery. The alterations in alpha(1)-AR signaling are associated with and may underlie the enhanced contractile response of the tail artery to adrenergic stimulation after I/R.
Seasholtz
T M
TM
Department of Pharmacology and Physiology, MCP Hahnemann School of Medicine, Philadelphia, Pennsylvania 19102, USA.
Cai
G
G
Wang
H Y
HY
Friedman
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D015424:Reperfusion; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013623:Tail / Q000098:blood supply
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D007294:Inositol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D009638:Norepinephrine