An approach to differentiate between noradrenaline-elicited contractile processes in the rat isolated aorta.
The aim of the present study was to assess the different processes contributing to the contraction induced by noradrenaline (NA, 1 mumol/l) in the rat isolated aorta. Pretreatment with maximally effective concentrations of nifedipine or cromakalim reduced the NA-induced contraction to 80 +/- 3.5% or 63 +/- 2.0%, respectively, without alteration of the shape of the response. After pretreatment with Mn2+, NA caused a transient phasic contraction followed by a sustained tonic component, comparable to the response obtained in "Ca2(+)-free" medium. Ryanodine--in the presence of extracellular Ca2(+)-caused a slight increase in resting tension, but did not modify the NA-induced contraction. In "Ca2(+)-free" medium the contraction elicited by NA consisted of a transient phasic and a sustained tonic component. The amplitude of the phasic contraction decreased exponentially with the time of exposure to "Ca2(+)-free" medium. The phasic component was identified as elicited by Ca2+ released from the sarcoplasmic reticulum (SR) by means of ryanodine. If Ca2+ depleted tissues (80 min in "Ca2(+)-free" solution) were exposed to Ca2+ in the presence of Mn2+ or cromakalim, the NA-induced phasic response was inhibited, suggesting that Mn2+ and cromakalim blocked the refilling of the store. It can be concluded that activation of alpha 1-adrenoceptors in the rat aorta by NA elicits Ca2(+)-entry processes which have a different sensitivity to nifedipine, cromakalim and Mn2+. The Ca2+ released from SR contributes about 20% to the overall contractile response. Our data suggest that the depleted SR can be refilled from the extracellular space via a direct cromakalim- and Mn2(+)-sensitive pathway.
Koch
P
P
Janssen Research Foundation, Neuss, Federal Republic of Germany.
Wilffert
B
B
Wilhelm
D
D
Peters
T
T
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019806:Cromakalim; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D011758:Pyrroles; D019806:Cromakalim; D012433:Ryanodine; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine