• DOI:10.1152/AJPHEART.00554.2002
• Corpus ID: 9068702

Pressure-dependent myogenic constriction of cerebral arteries occurs independently of voltage-dependent activation.

@article{Lagaud2002PressuredependentMC,
  title={Pressure-dependent myogenic constriction of cerebral arteries occurs independently of voltage-dependent activation.},
  author={Guy Lagaud and Nathalie Gaudreault and Edwin D. W. Moore and Casey van Breemen and Ismail Laher},
  journal={American journal of physiology. Heart and circulatory physiology},
  year={2002},
  volume={283 6},
  pages={
          H2187-95
        }
}

• G. Lagaud, N. Gaudreault, +2 authors I. Laher
• Published 1 December 2002
• Biology
• American journal of physiology. Heart and circulatory physiology

Pressure-induced decreases in arterial diameter are accompanied by membrane depolarization and Ca(2+) entry via voltage-gated Ca(2+) channels. Recent evidence also suggests the involvement of Ca(2+) sensitization of the contractile proteins. Both PKC and Rho kinase are candidate second messengers for the mediation of the sensitization process. We investigated the signaling pathways of pressure-induced decreases in rat cerebral artery diameter in vessels that were depolarized with a 60 mM potassium-physiological salt solution (KPSS). Arteries were mounted on a pressure myograph, and pressure-induced constrictions were recorded. In some experiments simultaneous changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) were recorded by using fura 2 fluorescence photometry. Pressure increases induced constriction with significant changes in [Ca(2+)](i) at high pressures (60-100 mmHg). The ratio of the change in diameter to change in [Ca(2+)](i) was greater for pressure-induced constriction compared with constriction produced by depolarization with 60 mM KPSS, suggesting that in addition to increases in [Ca(2+)](i), enhanced myofilament Ca(2+) sensitivity occurs during pressure-induced decreases in arterial diameter. Depolarizing the membrane with 60 mM KPSS increased [Ca(2+)](i) via a Ca(2+) influx pathway insensitive to PKC inhibition. Cerebral arteries were able to maintain their diameters in the continued presence of 60 mM KPSS. Pressure-induced constriction under these conditions was not associated with further increases in Ca(2+) but was abolished by selective inhibitors of PLC, PKC, and Rho kinase. We report for the first time that in rat cerebral arteries, pressure-induced decreases in arterial diameter are not only due to increases in voltage-gated Ca(2+) influx but also to accompanying increases in myofilament sensitivity to Ca(2+) mediated by PKC/Rho kinase activation.