High alpha 1-adrenoceptor occupancy decreases relaxing potency of nifedipine by increasing myosin light chain phosphorylation.
It has been proposed that the decreased potency of Ca2+ channel blockers to produce relaxation in vascular tissues contracted at high alpha 1-adrenoceptor occupancy may be caused by activation of spare receptors. Results from the present study using isolated strips of rabbit renal arteries contracted with the alpha 1-adrenoceptor agonist phenylephrine (PhE) support this hypothesis and provide a cellular explanation for the phenomenon. PhE at 1 microM activated only 23% of the total alpha 1-adrenoceptor pool but produced maximum stress while increasing the extent of myosin light chain phosphorylation to 35%. Activation of additional (spare) alpha 1-adrenoceptors with 100 microM PhE produced an additional increase in the extent of myosin light chain phosphorylation, which reached 45%, but did not produce an additional increase in stress above that produced by 1 microM PhE. A complete [PhE]-response curve revealed a quasihyperbolic dependency of stress on myosin light chain phosphorylation; i.e., a roughly linear relation existed at [PhE] values below that producing maximum stress, and at higher concentrations, phosphorylation was further increased but stress was not. Interestingly, the Ca2+ channel blocker nifedipine (0.1 microM) reduced the increases in myosin light chain phosphorylation produced by both 1 and 100 microM PhE by the same amount, approximately 12%. Nifedipine also reduced the increases in [Ca2+]i produced by 1 and 100 microM PhE by the same amount. However, nifedipine reduced the level of stress produced by 100 microM PhE by only 17%, whereas the level of stress produced by 1 microM PhE was reduced by 63%.(ABSTRACT TRUNCATED AT 250 WORDS)
- Copyright © 1993 by American Heart Association