Abstract 932: Temporal Changes In The Contribution Of Protein Kinase C Isoforms To Myogenic Constriction In Rat Posterior Cerebral Arteries
Background Cerebral arteries respond to an increase in intraluminal pressure with vasoconstriction, being referred to as myogenic tone. A number of studies have postulated the mechanisms involved in the development of myogenic tone; however, less information is available about how myogenic tone is maintained. The present study thus investigated the mechanisms underlying sustained myogenic constriction in isolated rat posterior cerebral arteries.
Methods and Results Long-term elevation of intraluminal pressure from 5 to 60 mmHg for 1 hr caused sustained constriction and [Ca2+]i elevation. In the presence of rottlerin, a PKCδ inhibitor, the pressure-induced constriction and [Ca2+]i elevation were gradually declined, and nearly abolished at the end of the 1-hr stimulation (sustained phase). In contrast, Gö 6976, a cPKC inhibitor, significantly inhibited the constriction for up to 5 min after the start of stimulation (initial phase), but had no effects on the [Ca2+]i elevation. The pressure stimulation induced small [Ca2+]i elevation even in the presence of nicaripine. Ruthenium red (RuR), a TRPV inhibitor, significantly inhibited the nicardipine-resistant [Ca2+]i elevation in the initial phase. However, slowly developing [Ca2+]i elevation was still observed in the sustained phase. In contrast, rottlerin had little effect on the initial phase, but significantly inhibited the sustained one. Moreover, the combination of RuR and rottlerin nearly abolished the nicardipine-resistant [Ca2+]i elevation. PKCα, γ, δ, and ε, but not PKCβ, were detected by immunohistochemisty in smooth muscle cells of rat posterior cerebral arteries.
Conclusions PKC isoforms have different roles in the development and maintain of the myogenic constriction in rat posterior cerebral arteries: cPKC (α and/or γ) mediates Ca2+ sensitization in the initial phase, whereas PKCδ mediates [Ca2+]i elevation via the activation of RuR-resistant cation channels in the sustained phase.