The cellular mechanisms underlying agonist-induced vasoconstriction have not been adequately characterised in human mesenteric arteries. Differences in vasoreactivity may arise with age, or as a consequence of the location within the particular vascular tree. We therefore examined the influence of these factors, as well as the relative contributions of distinct pools of intracellular and extracellular calcium (Ca²⁺), in the contractile responses of isolated human mesenteric arteries to three vasoconstrictive agonists- potassium chloride (KCl), U46619 and phorbol dibutyrate (PDBu).

The study was approved by the relevant local Ethics Committee, and full written informed consent was given by all patients. Mesenteric tissue was obtained at surgery from male (n = 14, age = 71±2.8) and female (n = 13, age = 56±4.4) patients undergoing resections for bowel carcinoma and was macroscopically normal. Mesenteric arteries (n = 72) were carefully dissected and loaded in a wire myograph and maintained at in vivo pressure (100mm/Hg) in oxygenated physiological saline solution (PSS) at 37 °C. Endothelial status was confirmed by exposure to acetylcholine (1 µM) following preconstriction with U46619 (1 µM). Vessels were then left to equilibrate in fresh PSS plus relevant vehicle (ethanol, 7 µl or distilled water, 35 µl). Control cumulative concentration-response curves (CCRC) were obtained to either KCl (0.1-100mM), U46619 (1-1000 nM) or PDBu (1-1000nM). After a maximal response was observed, the vessels were washed and allowed to equilibrate prior to repeating the CCRC under test conditions. For vessels re-exposed to KCl this comprised of 30min incubation with either the voltage-gated Ca²⁺ channel blocker nifedipine (N, 10 µM) or in Ca²⁺-free PSS. Vessels re-exposed to U46619 had a 30min incubation with either N (10 µM), the store-operated calcium channel blocker SK&F96365 (SKF, 50 µM) or in Ca²⁺-free PSS. Vessels re-exposed to PDBu had a 30min incubation in Ca²⁺-free PSS.

There were no differences in the responses to the agonists dependent on vessel diameter and age of the patients. Results from the test CCRCs are expressed as % of the maximal control for each agonist (Table 1), as mean ± SEM.

Table 1. * = p<0.01 compared to control CCRC, analysed via Wilcoxon Signed Ranks.