It is known that myogenic reactivity is a fundamental determinant of the relative constancy of blood flow through the cerebral artery. It is also known that acute alteration of pH significantly affects the cerebral circulation and, therefore, we investigated the effect of mechanism of action of intracellular
acidosis on myogenic tone in rabbit basilar artery. Myogenic tone was developed by imposed stretch of basilar artery and intracellular
acidosis induced by the bath application of 20 mmol/L
sodium acetate.
Sodium acetate caused a biphasic increase in myogenic tone. The initial component reached a peak quickly and then fell slowly to a lower steady-state significantly above basal tone. The
sodium acetate-induced increase in myogenic tone was completely inhibited by elimination of external Ca2+, or treatment of
nifedipine, but not with
gadolinium or
NPPB.
TEA (5 mmol/L) and
iberiotoxin (100 nmol/L) inhibited the
sodium acetate-induced increase in myogenic tone. In inside-out patch-clamp recordings, decreasing pH of the mock intracellular
solution from 7.4 to 6.9 markedly inhibited BKCa currents. Several inhibitors involved in Ca2+ sensitization pathways, 10(-6) mol/L
Y-27632, 5 x 10(-7) mol/L
calphostin C and 10(-5) mol/L
PD98059 had no effect on the
sodium acetate-induced increase in myogenic tone. These results suggest that intracellular
acidosis increases stretch-induced myogenic tone in rabbit basilar artery. Furthermore, voltage-dependent Ca2+ influx plays a key role in intracellular
acidosis-induced increase in myogenic tone and may be mediated, at least in part, by inhibition of BKCa.