Use-dependent decline in rat aorta sensitivity to contraction by potassium

Abstract

Aortic rings excised from rats at 12 weeks of age showed a decrease in responsiveness during repeated contraction by increasing potassium concentration. By comparison, aortic rings obtained from rats at 22 and 26 weeks exhibited less loss or an increase in responsiveness to high potassium concentration during repeated contraction. The decrease in responsiveness to potassium in aortae of young rats was not due to the extended interval of incubation of the tissue in vitro. Aortic rings incubated without stimulation for 4 h following a reference contraction showed no change in contractile response to potassium. However, the magnitude of loss in responsiveness to potassium did appear to be related to the potassium concentration and the length of time the tissues were exposed to the high potassium solutions. Contraction of the tissue at 60 versus 30 mM KCl or extending the interval in depolarizing solution from 15 to 60 min significantly enhanced the decline in tissue responsiveness to potassium. The interruption of a series of potassium-induced contractions by exposure of the tissue to contractile (serotonin, norepinephrine) or relaxant (acetylcholine, isoproterenol) stimuli had no effect on the loss in responsiveness to potassium. However, injection of the calcium channel agonist, Bay K 8644, into the incubation media restored responsiveness to potassium. Concentration–response curves indicated that both sensitivity and the maximal response to potassium were reduced in aortic rings repeatedly contracted with potassium. Bay K 8644 addition immediately following the control contraction significantly increased sensitivity and the maximal response to potassium compared with the control contraction. After tissues had been repeatedly contracted by potassium, Bay K 8644 restored tissue sensitivity and the maximum response to the control level. The results indicate that aortic tissues of young rats are subject to desensitization to potassium stimulation during repeated exposure in vitro. The restoration of tissue sensitivity by Bay K 8644 suggests that this desensitization centers on decreased effectiveness of the voltage-dependent mechanism for increasing intracellular concentration of free calcium and the activation of the contractile protein.Key words: concentration–response, depolarization, vascular smooth muscle, tension.