Protein kinase C alpha modulates microvascular reactivity in the human coronary and skeletal microcirculation.
BACKGROUND
Cardioplegic arrest (CP) and cardiopulmonary bypass (CPB) can lead to dysfunction in the coronary and skeletal microcirculation leading to impaired tissue perfusion. alpha-Adrenergic signaling pathways acting on these microcirculatory beds are thought to involve protein kinase C (PKC). We investigate here the role of the conventional PKCs in microvascular function in the setting of CP/CPB.


METHODS
Atrial and skeletal muscle was harvested from 30 patients undergoing cardiac surgery before and after CP/CPB. Microvessels were used for Western blotting and immunofluorescent staining against conventional PKCs. Microvascular constriction was assessed in pre- and post-CP/CPB samples in response to alpha-adrenergic stimulation with phenylephrine, with and without a PKC-alpha inhibitor or PKC-alpha activator. PKC activity was assessed in isolated microvessels.


RESULTS
Western blotting and immunostaining demonstrated only PKC-alpha in coronary and skeletal microvessels. CP/CPB diminished contractile responses to phenylephrine in coronary and skeletal samples. Inhibition of PKC-alpha reduced phenylephrine induced vasoconstriction in coronary and skeletal microvessels, whereas activation of PKC-alpha-augmented phenylephrine induced responses. PKC activity was decreased in coronary microvessels and to an even greater degree in skeletal microvessels after CP/CPB.


CONCLUSIONS
PKC-alpha is the predominant conventional PKC present in the human coronary and skeletal microcirculation. It likely plays a key role in alpha-adrenergic signaling in microvessels and in the vasomotor dysfunction after CP/CPB.
Sodha
Neel R
NR
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass, USA.
Feng
Jun
J
Clements
Richard T
RT
Bianchi
Cesario
C
Boodhwani
Munir
M
Ramlawi
Basel
B
Mieno
Shigetoshi
S
Khabbaz
Kamal R
KR
Sellke
Frank W
FW
D000368:Aged; D015153:Blotting, Western; D002196:Capillaries / Q000201:enzymology*; D003326:Coronary Circulation / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009206:Myocardium; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology
C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha