The influence of stretch on the role of potassium channels in the ß-adrenoceptor-mediated vasorelaxation in rat aorta N. Brahmadevara, A.M. Shaw & A. MacDonald, Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA.

Print abstract Search PubMed for: Brahmadevara N Shaw AM MacDonald A

As membrane stretch may activate K⁺ channels (Kirber et al., 1992), the present study was carried out to investigate the effect of stretch on the role of K⁺ channels in ß-adrenoceptor-mediated relaxation in rat isolated aorta.
Male Wistar rats (200 - 250 g) were stunned and killed by cervical dislocation before removal of the thoracic aorta. Ring preparations were suspended in Krebs physiological saline solution (PSS) gassed with 95/5 % O₂/CO₂ at 37 ^oC for isometric recording. The resting tension was adjusted to 1.5 g (low stretch) and 2.5 g (high stretch). Artery rings were pre-constricted with a sub-maximal concentration of phenylephrine (0.5µM) and the integrity of endothelium was checked with acetylcholine (1 µM) before carrying out cumulative concentration-response curves (CRCs) to isoprenaline. In inhibitor studies, tissues were incubated with inhibitor for 30 min before constricting. Values are mean±s.e.mean. Statistical analysis was carried out using Student's t test and ANOVA followed by post tests.

Phenylephrine induced concentration-dependent identical contractions in aortic rings at low and high stretch (pEC₅₀s: low, 6.82±0.05; high, 6.83±0.07, p>0.05, n=7). The size of the pre-constriction to phenylephrine was not affected by any of the K⁺ channel inhibitors.

Isoprenaline produced concentration-dependent identical relaxations in aortic rings at low and high stretch (pEC₅₀s: low, 7.60±0.03; high, 7.60±0.02; n=7). At high stretch, pre-treating the aortic rings with tetraethylammonium acetate (TEA, 10 mM), an inhibitor of Ca⁺² activated K⁺ channels, or iberiotoxin (IBTX, 100 nM), an inhibitor of large conductance Ca⁺² -activated K⁺ channels (BKca), inhibited the isoprenaline-induced relaxations (pEC₅₀s: IBTX, 6.84±0.04; TEA 10mM, 6.75±0.02, p<0.05, n=7). However, glibenclamide (10 µM), an inhibitor of K_ATP channels or 4-AP (10 µM), an inhibitor of voltage- dependent K⁺ (K_V) channels had no effect on isoprenaline-induced relaxation (pEC₅₀s: glibenclamide, 7.6±0.03, 4-AP, 7.6±0.03, p>0.05, n=6). At low stretch, none of the K⁺ channel inhibitors had an effect on isoprenaline-induced relaxation, as reported previously (Brahmadevara et al., 2002).

Forskolin produced concentration-dependent identical relaxations in aortic rings at low and high stretch (pEC₅₀s: low, 7.19±0.02; high, 7.18±0.01; n=6). At low stretch, IBTX (100 nM) had no effect on forskolin-induced relaxations (pEC₅₀: 7.23±0.03, p>0.05, n=6), whereas at high stretch there was a small shift of the forskolin CRC (pEC₅₀: 6.90±0.01, p<0.05, n=6).

In conclusion, these results show that at high, but not at low, stretch BK_ca channels are involved in ß-adrenoceptor-mediated relaxation in rat aorta, an involvement which is partly cAMP-dependent.

Brahmadevara, N. et al., (2002) Br J. Pharmacol., 137, 94P.
Kirber, M.T. et al., (1992) FEBS Letters, 297, 24-28.