Length-dependent activation and sensitivity in arterial ring segments

This study examines the effect of length on the dose-response (D-R) relationship and the effect of agonist concentration on the length-tension (L-T) relationship in vascular smooth muscle. The experiments used 2-mm rings from isolated segments of the dog anterior tibial artery. In D-R experiments the length (internal ring circumference) for maximum active force (Lmax) was determined first. D-R relationships were obtained from cumulative responses to increasing concentrations of norepinephrine (NE) or potassium (K+). L-T relationships were obtained from individual responses to a specific concentration of agonist as the ring was stretched in increments of L0 (the initial length for resting force). Dimensions of the arterial rings were measured with a video caliper. For NE and K+ stimulations at lengths equal to and less than Lmax: (a) The concentration for half maximal response (ED50) was lowest (most sensitive) at Lmax and increased significantly as length decreased from Lmax; (b) When the direction of length change was reversed, the direction of change in ED50 was reversed; and (c) The ED50 of repeated dose-response experiments at Lmax was not significantly different. For NE: (a) the ED50 decreased significantly when length was decreased to Lmax. The results of L-T experiments show Lmax is significantly longer for a low concentration of NE (10(-6) M) than for a high concentration (10(-5) M). With force normalized to the maximum force, the L-T curve is significantly lower, and the initial length for an active response was 80% longer for 10(-6) M than for 10(-5) M NE. It may be concluded that vascular smooth muscle has a length-dependent dose-response relationship and a concentration-dependent length-tension relationship.