Influence of increase in osmotic pressure with sucrose on relaxation and cyclonucleotides levels in isolated rat aorta

Abstract

The influence of increases in osmolarity by addition of sucrose were investigated on relaxation and changes in adenosine 3':5'-cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in isolated rat aortic rings. Isoprenaline-mediated relaxations were attenuated in hypertonic (341+/-0.4 mOsmol) (mean+/-S.E.M.) solution. The concentration-response curve to isoprenaline was displaced to the right. The EC(50) (0.16+/-0.05 vs. 1.14+/-0.5 microM) significantly (n=6; P<0.05) increased without any changes to the maximum response. Hypertonic solution also attenuated methacholine-mediated relaxations resulting in a significant increase in the EC(50) (0. 28+/-0.04 vs. 0.52+/-0.04 microM) and reduced the maximal response (73+/-5% vs. 51+/-8%). In contrast, an increase in tonicity did not have any influence on sodium nitroprusside, forskolin or pinacidil concentration-response curves. Hypertonic solution also did not affect either basal cyclic AMP or cyclic GMP production. In addition, an increase in osmolarity did not affect isoprenaline-stimulated increases in the levels of cyclic AMP. However, an increase in the tonicity of Krebs solution significantly inhibited methacholine-stimulated (58%-34%) accumulation of cyclic GMP. The present data indicated that an increase in the tonicity of Krebs solution impaired endothelium-dependent relaxation and the associated increase in cyclic GMP production without affecting basal levels of this nucleotide. The inhibitory effects of high osmolarity on beta-adrenoceptor-mediated relaxation did not appear to be due to a reduction in cyclic AMP generation, or the result of inhibition of pinacidil-sensitive K(ATP)(+) channels. Moreover, an increase in the tonicity of Krebs solution did not influence relaxation induced by direct activation of adenylate cyclase or guanylate cyclase by forskolin and sodium nitroprusside, respectively.