Age-dependence of the effects of pinacidil on rat aorta

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Abstract
The effect of the K+ channel opening drug, pinacidil, has been examined on aortic ring preparations from young (2 months) and aged (> 24 months) rats. The potency (neg log IC50) values for pinacidil in relaxing K+ (20 mM)-contracted preparations were in the range expected for its K+ channel opening (hyperpolarizing) effects but were not significantly different between young (6·34) and aged (6·31) rats. Thus, ageing does not affect the drug’s potency as a K+ channel opening drug. The more marked depression of the maximum response to noradrenaline by pinacidil (10 μM) in aged rats (85% reduction) compared with young rats (43% reduction), reflected a reduced α-adrenoceptor reserve for noradrenaline in preparations from aged rats. Pinacidil, in concentrations greater than 10 μM, was able to relax preparations contracted with 80 mM K+ suggesting that it may have a second mechanism which does not involve hyperpolarization. It was more potent in producing this effect on the preparations from aged rats.