Wanstall J C, O'Donnell S R, Zeng X P
Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Brisbane, Australia.
J Pharm Pharmacol. 1989 Sep;41(9):641-3. doi: 10.1111/j.2042-7158.1989.tb06548.x.
The effect of the K+ channel opening drug, pinacidil, has been examined on aortic ring preparations from young (2 months) and aged (greater than 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 microM) in aged rats (85% reduction) compared with young rats (43% reduction), reflected a reduced alpha-adrenoceptor reserve for noradrenaline in preparations from aged rats. Pinacidil, in concentrations greater than 10 microM, 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.
已研究了钾通道开放药物吡那地尔对年轻（2个月）和老年（超过24个月）大鼠主动脉环标本的作用。吡那地尔在舒张钾（20 mM）收缩标本中的效价（负对数IC50）值在其钾通道开放（超极化）效应预期范围内，但年轻（6.34）和老年（6.31）大鼠之间无显著差异。因此，衰老并不影响该药物作为钾通道开放药物的效价。与年轻大鼠（降低43%）相比，老年大鼠（降低85%）中吡那地尔（10 microM）对去甲肾上腺素最大反应的抑制更为明显，这反映出老年大鼠标本中去甲肾上腺素的α-肾上腺素能受体储备减少。浓度大于10 microM的吡那地尔能够舒张由80 mM钾收缩的标本，表明它可能具有不涉及超极化的第二种机制。它对老年大鼠标本产生这种效应的效力更强。
