Arterial smooth muscle constriction in response to pressure, i.e., myogenic tone, may involve
calcium-dependent and
calcium-sensitization mechanisms.
Calcium sensitization in vascular smooth muscle is regulated by
kinases such as PKC and
Rho kinase, and activity of these
kinases is known to be altered in cardiovascular disorders. In the present study, we evaluated the relative contribution of PKC and
Rho kinase to myogenic tone in cerebral arteries in
hypertension. Myogenic tone and arterial wall
calcium in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were measured simultaneously, and the effect of PKC and
Rho kinase inhibitors on myogenic tone was evaluated. SHR arteries showed significantly greater myogenic tone than WKY arteries. Pressure/wall tension-arterial wall
calcium curves showed a hyperbolic relation in WKY rats, but the curves for SHR arteries were parabolic. Myogenic tone was decreased by the
Rho kinase inhibitors
Y-27632 and
HA-1077, with a significantly greater effect in SHR than in WKY arteries. Reduction in myogenic tone produced by the PKC inhibitor
bisindolylmaleimide I in WKY and SHR arteries was significantly less than that produced by
Rho kinase inhibition. The pressure-dependent increase in myogenic tone was significantly decreased by
Y-27632, and the decrease was markedly greater than that produced by
bisindolylmaleimide I in SHR arteries. In WKY arteries, the pressure-dependent increase in myogenic tone was decreased to a similar extent by
Y-27632 and
bisindolylmaleimide I. These results suggest greater myogenic tone with increased
calcium sensitization in SHR arteries, largely because of
Rho kinase activation, with a minor contribution of PKC activation.