Differences in sensitivity of rat mesenteric small arteries to agonists when studied as ring preparations or as cannulated preparations.
1. Pharmacological experiments on vascular tissue are normally performed on isometric ring or strip preparations. The aim of this study was to compare the isometric characteristics with the characteristics obtained if vessels were examined under the more physiologically appropriate isobaric condition. 2. Rat mesenteric small arteries were mounted either on two steel wires for isometric force measurement (wire-myograph) or cannulated for measurement of the internal diameter under isobaric conditions (pressure-myograph). 3. The passive pressure-diameter characteristics of the small arteries were similar on the wire- and pressure-myograph (using the Laplace relation to convert wall tension-internal circumference data from the wire-myograph to effective pressure-diameter characteristics). 4. In cumulative concentration-response experiments with noradrenaline and phenylephrine, the threshold concentration was 8-10 times lower, and the EC50-concentration was 4-5 times lower, in the pressure myograph compared to the wire-myograph. Thus vessels were not only more sensitive on the pressure myograph, but the slopes of the concentration-response curves were less steep. Similar experiments with vasopressin also showed this difference in the threshold-concentration and slope, but EC50 concentrations were similar. 5. Cumulative concentration-response experiments with K+ showed no difference either in EC50 or in slope on the wire- and pressure-myographs. 6. On the wire-myograph, some vessels were stretched longitudinally (to mimic the longitudinal stretch which had to be used in the pressure-myograph to avoid buckling). Such stretch did not affect the passive characteristics. 7. The differences between the EC50 determined on the wire- and pressure-myographs as regards noradrenaline and phenylephrine were eliminated when neuronal noradrenaline uptake was inhibited by denervation. However, the slope of the concentration-response curves on the wire-myograph was not affected by denervation.8. When vessels were exposed to cocaine (3 MicroM) the noradrenaline concentration-response curves were the same on the wire- and pressure-myographs as regards both EC50 and slope.9. On the wire-myograph, the calcium antagonist, methoxyverapamil, (D600) reduced the maximal contractile effect of noradrenaline by 50%, but on the pressure-myograph D600 did not affect the maximal response.10. The present results show that results obtained from vascular tissue under isometric conditions may differ substantially from the characteristics which would be obtained under isobaric conditions.
Buus
N H
NH
Danish Biomembrane Research Centre, Aarhus University.
VanBavel
E
E
Mulvany
M J
MJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology; D004576:Electromyography / Q000187:drug effects; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000294:innervation; D009121:Muscle Denervation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D005711:Gallopamil; D003042:Cocaine; D011188:Potassium; D009638:Norepinephrine