title: Functional study on the effects of nifedipine, cromakalim, and the absence of extracellular Ca2+ on alpha 1-adrenoceptor-mediated excitation-contraction coupling in isolated rat portal vein: comparison with depolarization-mediated excitation-contraction coupling.
abstract: The effects of Ca(2+)-entry blockade by nifedipine, K+ channel opening by cromakalim, and of omitting extracellular Ca2+ on the contractile response elicited by a supramaximum concentration of the "full" and selective alpha 1-adrenoceptor agonist phenylephrine (10(-4) M) were compared with those elicited by a supramaximal concentration of KCl (50 mM) in isolated rat portal vein. The contractile response to phenylephrine appeared to be biphasically composed of an early "transient" phase and a slowly developing "sustained" phase that reached maximum values after 30 s and 5 min after initiation of contraction, respectively. The contractile response to KCl (50 mM) exhibited a triphasic pattern consisting of "spike," "transient", and "sustained" components that peaked after 8 s, 25 s, and 10 min, respectively. Nifedipine was able to eliminate all components of the contractions in response to both phenylephrine and KCl almost completely. Nifedipine was approximately 10 times more potent at suppressing the slowly developing sustained components of the contractions in response to both stimuli than the early transient components. The spontaneous myogenic contractions were inhibited by nifedipine with intermediate potency. Cromakalim, in contrast to nifedipine, selectively eliminated the early transient components of the contractions in response to both phenylephrine and KCl. The sustained components of the contractions in response to both stimuli were relatively resistant to K+ channel opening, although higher concentrations (> 1 microM) of cromakalim were capable of antagonizing the sustained response to phenylephrine accompanied by oscillations in tone. Cromakalim was most potent in counteracting spontaneous myogenic contractions. When phenylephrine and KCl were added with or without external Ca2+ after different periods of equilibration in nominally Ca(2+)-free medium, different washout kinetics for the different components of the contractions in response to both stimuli were observed. The early transient phases of tension development in response to both stimuli were completely lost after approximately 6 min of equilibration in nominally Ca(2+)-free medium, whereas the slowly developing sustained components of the contractions were immediately lost after the change to nominally Ca(2+)-free medium. Externally added Ca2+, when administered together with phenylephrine or KCl after the preparations had been exposed for different times to nominally Ca(2+)-free medium, could not restore the early transient components.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Schwietert
authors.forename: D
authors.initials: D
authors.lastname: Wilhelm
authors.forename: B
authors.initials: B
authors.lastname: Wilffert
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019806:Cromakalim; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
chemical_list: D001578:Benzopyrans; D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D011942:Receptors, Adrenergic, alpha; D019806:Cromakalim; D010656:Phenylephrine; D011189:Potassium Chloride; D009543:Nifedipine; D002118:Calcium