Pre-junctional stimulatory and post-junctional inhibitory effects of pinacidil in the isolated main pulmonary artery of the rabbit under different experimental conditions.
Low frequency (2Hz) nerve-stimulation induced [3H]noradrenaline ([3H]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 x 10(-5)M; corticosterone, 5 x 10(-5), with parallel measurements of post-junctional contractile responses. The K+ ATP-channel opener pinacidil (10(-6)-10(-4)M), slightly potentiated the nerve-evoked release of [3H]NA which failed to show close concentration-dependency. Large concentration of pinacidil (10(-4)M) increased the ratio of [3H]NA release from 0.99 +/- 0.02 to 1.29 +/- 0.05; P < 0.0005). On the other hand, pinacidil inhibited the nerve-evoked contractions in a concentration-dependent manner. 10(-4)M caused nearly 70% inhibition of contractile response. The pre- and post-junctional effects of pinacidil were studied under the following experimental conditions: (1) exogenously applied I-NA; (2) excess K+; (3) 'L-type' Ca(2+)-channel activation (BAY K 8644); (4) K(+)-channel inhibition (4-AP); and (5) Na(+)-pump inhibition/reactivation. Pinacidil (10(-4)M) retained its marginal NA-release stimulatory effect in all cases. However, pinacidil inhibited the contraction of smooth muscle, although to a different extent, in all of the experimental conditions used in our study.
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
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D
Rácz
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Zillikens
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Forstreuter
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Nagykáldi
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Magyar
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TL
Török
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D009119:Muscle Contraction / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D020110:Pinacidil; D015221:Potassium Channels / Q000502:physiology; D011651:Pulmonary Artery / Q000294:innervation / Q000502:physiology*; D011817:Rabbits; D009435:Synaptic Transmission
D000959:Antihypertensive Agents; D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil; D009638:Norepinephrine