Dependence of Ca2+ sensitivity of arterial contractions on history of receptor activation

Dependence of Ca2+ sensitivity of arterial contractions on history of recep tor activation. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1661-R1668, 1999. -Stimulation of receptors causing arterial contraction may also caus e attenuation of cell responsiveness to stimuli. This study tested the hypo thesis that attenuation of receptor-induced contractions involves Ca2+ dese nsitization. Renal artery rings were pretreated with 10 mu M phenylephrine (PE), relaxed with PE washout (plus phentolamine), and then activated by hi stamine (HA). Pretreatment for 30 min resulted in a rightward shift in the concentration-contraction curve to HA by similar to 1/2 log without a reduc tion in the slope or maximum response. For example, control and PE-pretreat ed tissues responded to 0.56 mu M HA with strong (0.95 F/F-o) and weak (0.1 6 F/F-o) contractions, respectively, where F/F-o represents contractile for ce. This reduced reactivity was completely reversed within 90 min. In fura- loaded tissues, PE pretreatment caused less of a rightward shift in the HA concentration-intracellular free Ca2+ concentration ([Ca2+](i)) curve than in the HA concentration-contraction curve. A dissociation between force and [Ca2+]i was also produced when KCI was used instead of HA. These data sugg est that the reduced reactivity produced by PE pretreatment involved, in pa rt, a reduction in the ability of HA to increase the Ca2+ sensitivity of co ntractions. These data support the hypothesis that the degree of stimulus-i nduced Ca2+ sensitization of contractions is dependent on the history of re ceptor activation.