Distinct roles of protein kinase C isoforms in myogenic constriction of rat posterior cerebral arteries.
The involvement of protein kinase C (PKC) in myogenic constriction at physiological intraluminal pressure was investigated in rat posterior cerebral arteries. Changes in constriction and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in fura 2-loaded arterial segments by pressurized arteriography. When intraluminal pressure was raised from 5 to 60 mmHg and maintained for 60 min, sustained constriction and [Ca(2+)](i) elevation were elicited. The constriction and [Ca(2+)](i) at 60 mmHg gradually declined in the presence of RO31-8220, a general PKC inhibitor, and rottlerin, a PKCdelta inhibitor. In contrast, Gö6976, a conventional PKC inhibitor, significantly diminished the constriction with no inhibition on the [Ca(2+)](i). In the presence of nicardipine, the pressure stimulation to 60 mmHg still produced a small sustained [Ca(2+)](i) elevation. The nicardipine-insensitive [Ca(2+)](i) elevation gradually declined in the presence of rottlerin, and it was nearly abolished by ruthenium red. Immunohistochemical analysis showed positive staining for PKCalpha, gamma, delta, and epsilon, but not PKCbeta, in smooth muscle cells of rat posterior cerebral arteries. These results suggest distinct roles of PKC isoforms in myogenic constriction: conventional PKC mediates Ca(2+) sensitization, whereas PKCdelta mediates sustained [Ca(2+)](i) elevation via the activation of cation channels, resulting in sustained constriction.
Kashihara
Toshihide
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Nakayama
Koichi
K
Ishikawa
Tomohisa
T
D000792:Angiography / Q000379:methods; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016257:Fura-2; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D020769:Posterior Cerebral Artery / Q000378:metabolism*; D011312:Pressure; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction
D020033:Protein Isoforms; D011493:Protein Kinase C; D002118:Calcium; D016257:Fura-2