Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries

FIGURE 1. Maximum and highmolar KCl‐induced contractions of porcine renal interlobar and coronary arteries. In (A), values are maximum contractions following application of EFS and agonists as indicated in control groups, regardless at which frequency or agonist concentration they occured (for concentrations, see Table 1). In (B), contractions induced by highmolar KCl are expressed in mN. EFS‐ and agonist‐induced contractions in all other diagrams have been calculated as percentage of contractions induced by 80 mM KCl. KCl‐induced contractions were assessed before application of DMSO (in controls) or picotamide. Thus, contractions shown for controls and picotamide were in fact assessed under the same conditions, i.e. withouth DMSO or picotamide, but here shown separately to demonstrate that overall contractions were similar in picotamide and control groups. Shown are all single values from all experiments performed for frequency response curves and concentration response curves in Figures 2, 3, 4, 5 together with means (=bars). Contractions were obtained under the presence of DMSO (controls, solvent for picotamide). As three concentrations of picotamide were examined for EFS‐induced…

FIGURE 2. Effects of picotamide on U46619‐, EFS‐, and noradrenaline‐induced contractions in renal interlobar (A, C–F) and coronary (B) arteries. Contractions were induced by cumulative concentrations of U46619, different frequencies of EFS, or by cumulative concentrations of noradrenaline in interlobar arteries, 30 min following administration of picotamide or solvent (controls). Shown are means ± SD in frequency response curves (#p < .05 for control vs. picotamide by two‐way ANOVA, and p values for whole groups from one‐way ANOVA in inserts), and all single Emax values and frequencies inducing 50% of the maximum EFS‐induced contraction (Ef50) or EC50 values for noradrenaline from all experiments (calculated by curve fitting) in scatter plots (p value from paired Student's t‐test), from experiments using tissues from n = 5 animals in A, B and D‐F, and n = 6 animals in C. For each single experiment, tissue from one animal was allocated to the control and the picotamide group, which were examined in the same experiment.

FIGURE 3. Effects of picotamide on α1‐adrenergic and cholinergic contractions in renal interlobar and coronary arteries. Contractions were induced by cumulative concentrations of α1‐adrenergic agonists (phenylephrine, methoxamine) or cholinergic agonists (methacholine, carbachol) in interlobar arteris (A, B) or coronary arteris (C‐F), 30 min following administration of picotamide (300 µM) or solvent (controls). Shown are means ±SD in concentration response curves (# p < .05 for control vs. picotamide by two‐way ANOVA, and p values for whole groups from one‐way ANOVA in inserts), and all single Emax and EC50 values for single experiments (calculated by curve fitting) in scatter plots (p value from paired Student's t‐test), from experiments using tissues from n = 5 animals in B, D, E and F, and n=6 animals in A and C. For each single experiment, tissue from one animal was allocated to the control and the picotamide group, which were examined in the same experiment. In one of six experiments performed for the series in (A), curve fitting revealed an EC50 value of 756 µM for phenylephrine in the control group, which has been omitted from the diagram and calculations. For each single…

FIGURE 4. Effects of picotamide on serotonin‐induced and purinergic contractions in renal interlobar and coronary arteries. Contractions were induced by cumulative concentrations of serotonin (A, B) and α,β‐methylene‐ATP and ATP (C, D) in interlobar arteries (A, C) or coronary arteries (B, D), 30 min following administration of picotamide (300 µM) or solvent (controls) (with the exception of (D), where not picotamide was included in experiments with α,β‐methylene‐ATP). Shown are means ±SD in concentration response curves (#p < .05 for control vs. picotamide by two‐way ANOVA, and p values for whole groups from one‐way ANOVA in inserts), and (with one exception) all single Emax and EC50 values for single experiments (calculated by curve fitting) in scatter plots (p value from paired Student's t‐test), from experiments using tissues from n = 5 animals in B‐D, and n = 6 animals in A.

FIGURE 5. Effects of picotamide on angiotensin‐II‐, endothelin‐1‐, and vasopressin‐induced contraction in renal interlobar and coronary arteries. Contractions were induced by cumulative concentrations of angiotensin‐II (A, B), endothelin‐1 (C, D), or vasopressin (E, F) in interlobar arteries (A, C, E) or coronary arteries (B, D, F), 30 min following administration of picotamide (300 µM) or solvent (controls), with the exception of (E). Shown are means ± SD in concentration response curves (#p < .05 for control vs. picotamide by two‐way ANOVA, and p values for whole groups from one‐way ANOVA in inserts), and all single Emax and EC50 values for single experiments (calculated by curve fitting) in scatter plots (p value from paired Student's t‐test), from experiments using tissues from n = 5 animals in B, E, and F, n = 6 animals in A, n = 8 animals in D, and n = 10 animals in C. For each single experiment, tissue from one animal was allocated to the control and the picotamide group, which were examined in the same experiment.