Differences and similarities in the noradrenaline- and caffeine-induced mechanical responses in the rabbit mesenteric artery.
1. The properties of noradrenaline (NA)-induced and caffeine-induced contractions in the rabbit mesenteric artery were investigated and compared, using intact and skinned muscles.2. NA (> 10(-7) M) depolarized the membrane and reduced the membrane resistance. Increased concentrations of NA (> 10(-5) M) rarely produced oscillatory potential changes yet consistently produced oscillatory contractions which were abolished by pre-treatment with prazosin or Ca-free solution. Application of low concentrations (0.5 mM) of caffeine hyperpolarized the membrane and high concentrations (5 mM) depolarized the membrane.3. NA- and caffeine-induced contractions, but not a K-induced contraction, could be recorded in Ca-free, EGTA (2 mM) containing solution.4. In Ca-free, EGTA containing solution, repetitive applications of NA or caffeine led to a cessation of contractions. Responses persisted longer with applications of NA than with caffeine. In Na-free, Ca-free solution, the contractions evoked by both agents applied repetitively persisted much longer than those evoked in the presence of [Na](o).5. When 50 mug/ml. saponin was applied for 8 min, NA produced only one contraction and with application of 10(-6) M-Ca, only a small contraction was evoked. When saponin was applied for 20 min, NA produced no contraction while 10(-6) M-Ca produced a large contraction, indicating that NA produced a contraction under conditions of incomplete skinning, while caffeine consistently released Ca from incompletely and completely skinned muscles.6. After 20 min of saponin treatment (50 mug/ml.), the pCa-tension relationship could be measured. The minimum concentration of Ca required to produce the contraction was just over 10(-7) M, and the maximum contraction occurred with 3 x 10(-6) M-Ca and was greater than that produced by 128 mM-K in intact muscles. The sigmoidal relationship with this rabbit tissue was sharper than that observed in the guinea-pig mesenteric artery. Application of 10 mM-procaine and 10 mM-caffeine slightly inhibited the pCa-tension relationship.7. In skinned muscles, the amount of stored Ca was estimated from the amplitude of the caffeine-induced contraction. Addition of NA (10(-5) M) with 10(-6) M-Ca had no effect on the caffeine-induced contraction. A reduction of Na from 10 mM to zero in the relaxing solution slightly suppressed the caffeine - induced contraction, i.e. there was a slight inhibition of Ca accumulation.8. Thus, different mechanisms are involved in the NA- and caffeine-induced activations, but both agents do release Ca stored in the same site. Release of Ca from the store site by NA requires the presence of an intact muscle membrane with adrenoceptors but this is not the case with caffeine. The different mechanical responses to NA or caffeine may also relate to the behaviour of Ca; i.e. Ca may be extruded into the extracellular space in the presence of caffeine, while this ion may be extruded and to some extent, re-accumulate into the store site in the presence of NA. The oscillatory contraction evoked by treatment with NA is discussed in relation to the activation of a Ca-induced Ca-release mechanism in the store site.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology
D012503:Saponins; D002110:Caffeine; D004533:Egtazic Acid; D002118:Calcium; D009638:Norepinephrine