Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries

Abu Ahmed, Christopher M. Waters, Charles W. Leffler, Jonathan H. Jaggar

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Mechanisms that underlie autoregulation in the newborn vasculature are unclear. Here we tested the hypothesis that in newborn porcine cerebral arteries intravascular pressure elevates wall tension, leading to an increase in intracellular calcium concentration ([Ca2+]i) and a constriction that is opposed by pressure-induced K+ channel activation. Incremental step (20 mmHg) elevations in intravascular pressure between 10 and 90 mmHg induced an immediate transient elevation in arterial wall [Ca2+]i and a short-lived constriction that was followed by a smaller steady-state [Ca2+]i elevation and sustained constriction. Pressures between 10 and 90 mmHg increased steady-state arterial wall [Ca2+]i between ∼142 and 299 nM and myogenic (defined as passive-active) tension between 25 and 437 dyn/cm. The relationship between pressure and myogenic tension was strongly Ca2+ dependent until forced dilation. At low pressure, 60 mM K+ induced a steady-state elevation in arterial wall [Ca2+]i and a constriction. Nimodipine, a voltage-dependent Ca2+ channel blocker, and removal of extracellular Ca2+ similarly dilated arteries at low or high pressures. 4-Aminopyridine, a voltage-dependent K+ (K v) channel blocker, induced significantly larger constrictions at high pressure, when compared with those at low pressure. Although selective Ca2+-activated K+ (KCa) channel blockers and intracellular Ca2+ release inhibitors induced only small constrictions at low and high pressures, a low concentration of caffeine (1 μM), a ryanodine-sensitive Ca2+ release (RyR) channel activator, increased Kca channel activity and induced dilation. These data suggest that in newborn cerebral arteries, intravascular pressure elevates wall tension, leading to voltage-dependent Ca2+ channel activation, an increase in wall [Ca2+]i and Ca2+-dependent constriction. In addition, pressure strongly activates Kv channels that opposes constriction but only weakly activates Kca channels.

Original languageEnglish
Pages (from-to)H2061-H2069
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number5 56-5
DOIs
StatePublished - Nov 2004

Keywords

  • Calcium-activated potassium channel
  • Intracellular calcium
  • Intravascular pressure
  • Voltage-dependent potassium channel
  • Wall tension

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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