Comparison of Cumulative and Non-Cumulative Administration of Vasoactive Agents in Arterial Smooth Muscle Responsesin Vitro

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Abstract
Two methods of determining concentration-response curves were compared in isolated endothelium-intact mesenteric arterial rings from Wistar rats: arterial contractile and relaxation responses were elicited by adding compounds cumulatively or introducing a single concentration at a time (non-cumulative method). The contractile responses induced by high concentrations of K+ (20-125 mM) were comparable between the two methods, whether or not the responses were elicited in the presence of phentolamine (10 microM) and atenolol (10 microM). Noradrenaline (1 nM-10 microM) likewise induced similar contractions regardless of method of administration, the only exception being the highest concentration (100 microM) which produced lower contractile force when added directly upon resting tension than after cumulative administration. This difference was abolished by atenolol (10 microM). Arterial smooth muscle relaxations induced by endothelium-dependent (acetylcholine 1 nM-10 microM) and -independent agents (nitroprusside 1 nM-1 microM, isoprenaline 10 nM-100 microM) were similar whether the relaxants were added in a cumulative fashion or in a single concentration introduced upon each precontraction. Thus, cumulative and non-cumulative administration of contractile and relaxing agents give quite comparable results. We conclude that the cumulative method is a reliable and time-saving way of studying vascular smooth muscle responses in vitro.