Decreased myogenic reactivity in skeletal muscle arterioles after hypothermic cardiopulmonary bypass.
Cardiopulmonary bypass (CPB) is associated with a generalized defect in the intrinsic control of vascular smooth muscle. To determine if myogenic reactivity of skeletal muscle arterioles was altered by CPB, sheep (n = 7) were placed on hypothermic CPB (27 degrees C) for 90 min and hearts were arrested by cold blood cardioplegia ([K+] = 25 mM) for 60 min. Arterioles (70-180 microns) were isolated from the gracilis muscle before (control) and 15 min after CPB. In vitro arteriolar responses were studied with video-microscopy. Myogenic reactivity was examined to stepwise increases in intraluminal pressure from 10 to 100 mm Hg. Mean arterial pressure was decreased from 80 +/- 15 prior to CPB to 55 +/- 4 mm Hg (P < 0.01) 15 min after CPB. Myogenic contraction was observed in control vessels and was markedly attenuated by the protein kinase C inhibitor staurosporine (P < 0.01). CPB decreased myogenic contraction and shifted the pressure-diameter relation upward, suggesting a decrease in the intrinsic tone (both P < 0.05 vs control). CPB reduced contractile responses to the alpha 1-adrenoceptor agonist phenylephrine from -43 +/- 7% to -23 +/- 5% (P < 0.01) and the protein kinase C activator 12-deoxyphorbol 13-isobutyrate 20-acetate (phorbol ester) from -64 +/- 6% to -38 +/- 16% (P < 0.01). CPB-associated decrease in myogenic reactivity of skeletal muscle arterioles is likely due to alterations in protein kinase C and/or downstream signal transduction. This may account in part for reduction in systemic vascular resistance and hypotension associated with CPB.
Wang
S Y
SY
Department of Surgery, Beth Israel-Deaconess Medical Center, Boston, Massachusetts, USA.
Stamler
A
A
Li
J
J
Johnson
R G
RG
Sellke
F W
FW
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D001026:Coronary Artery Bypass; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D012756:Sheep; D019311:Staurosporine / Q000494:pharmacology; D014661:Vasoconstriction
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D010703:Phorbol Esters; D010656:Phenylephrine; C047907:12-deoxyphorbol-13-isobutyrate-20-acetate; D011493:Protein Kinase C; D019311:Staurosporine