ROLE OF WALL TENSION IN THE VASOCONSTRICTOR RESPONSE OF CANNULATED RAT MESENTERIC SMALL ARTERIES

1. We have studied the influence of mechanical loading conditions on the responses of cannulated rat mesenteric small arteries to noradrenaline, vasopressin and potassium. 2. The cross-sectional area (CSA) of vessels was continuously monitored. Isometric loading (CSA-controlled conditions) or isobaric loading (pressure-controlled conditions) was achieved by feedback adjustment of the distending pressure. 3. Noradrenaline (0.3 mu M) and vasopressin (0.05 u l(-1)) induced myogenic responsiveness, resulting in a constant or declining CSA with increasing pressure. Potassium (32 mM) induced weak myogenic responsiveness. 4. At a constant pressure of 60 cmH(2)O, noradrenaline and vasopressin concentration-response curves were graded, the concentration-response curves of individual vessels being extended over two to three decades. Sensitivity to the vasoconstrictors, expressed as pD(2) values (-log(10) EC(50)), averaged 6.45 +/- 0.18 log M and 1.27 +/- 0.20 log u l(-1) for the noradrenaline and vasopressin concentration-response curves respectively. The isobaric pD(2) for K+ was 1.54 +/- 0.07 log M. 5. During CSA-controlled conditions, noradrenaline and vasopressin induced all-or-none responses to stretch. Potassium induced graded responses to stretch. 6. During CSA-controlled conditions, noradrenaline and vasopressin concentration-response curves also showed all-or-none behaviour. Almost the full response occurred through only a doubling of the concentration. pD(2) values were 6.88 +/- 0.38 log M (noradrenaline) and 1.87 +/- 0.43 log u l(-1) (vasopressin). Isometric vessels were significantly more sensitive to noradrenaline and vasopressin than isobaric vessels. Isometric K+ curves were gradual. pD(2) was 1.54 +/- 0.07 log M, a value not different from the isobaric value. 7. These findings can be explained by assuming that agonist sensitivity is wall tension dependent, such that sensitivity increases with increasing wall tension. This concept accounts for partial regulation of wall tension during pressure-controlled conditions, as well as instability due to a positive feedback loop of active tension development and tension-induced sensitization during CSA-controlled conditions.