title: 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.
authors.affiliation: Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, Health Sciences Centre, St. John's, Newfoundland, Canada. rtabrizc@morgan.ucs.mun.ca
authors.forename: R
authors.initials: R
authors.lastname: Tabrizchi
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009997:Osmotic Pressure; D020110:Pinacidil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D006982:Hypertonic Solutions; D018721:Muscarinic Agonists; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D009599:Nitroprusside; D005576:Colforsin; D013395:Sucrose; D020110:Pinacidil; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol