title: Effects of nitric oxide donors on vascular smooth muscles depend on a type of vascular smooth-muscle preactivation.
abstract: The abilities of such therapeutic nitrovasodilators as sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) to dilate vascular smooth muscles (VSM) and affect intracellular calcium concentration level ([Ca2+]i) in a rat tail artery were tested under different types of preactivation. To shed light on mechanisms underlying possible differences in the action of these two nitric oxide (NO) donors, simultaneous measurements of [Ca2+]i and contractile force were done. All vascular rings were precontracted either using a high-K+-Krebs solution or phenylephrine (PE). It was shown that the effect of both NO donors strongly depended on a type of VSM preactivation. The EC50 for GTN under K+ stimulation of VSM comprised (2.48 +/- 1.6) x 10(-5) M, whereas the mean EC50 under PE stimulation was (3.05 +/- 2.3) x 10(-4) M (p < 0.05, n = 9). The EC50 for SNP under K+ stimulation of VSM comprised (1.09 +/- 0.47) x 10(-7) M, whereas the EC(50) under PE stimulation was (8.01 +/- 2.4) x 10(-6) M (p < 0.05, n = 9). GTN demonstrated a significant discrepancy in the magnitude of changes in [Ca2+]i and related VSM relaxant responses, indicating the ability of GTN to relax VSM in the absence of a proportional decrease in [Ca2+]i. The main peculiarity of SNP action under K+ stimulation as compared to PE stimulation was the transient decrease in [Ca2+]i while relaxation was sustained. Therefore, both NO donors demonstrated their ability to produce vasorelaxation as a result of an alteration in myofilament calcium sensitivity. These data clearly indicate that the sensitivity of VSM to NO donors is higher under K+ depolarization than that seen under PE stimulation, indicating that Ca2+ entry through voltage-operated calcium channels is more sensitive to NO as compared to calcium mobilization by means of Ca2+ entry through receptor- operated calcium channels or intracellular Ca2+ release, or both.
authors.affiliation: Department of Experimental Therapy, Institute of Pharmacology and Toxicology, Kiev 03057, Ukraine.
authors.forename: V V
authors.initials: VV
authors.lastname: Lehen'kyi
authors.forename: S N
authors.initials: SN
authors.lastname: Zelensky
authors.forename: A V
authors.initials: AV
authors.lastname: Stefanov
authors.forename: A I
authors.initials: AI
authors.lastname: Soloviev
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007552:Isotonic Solutions / Q000008:administration & dosage; D008297:Male; D023421:Models, Animal; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D005996:Nitroglycerin / Q000008:administration & dosage; D009599:Nitroprusside / Q000008:administration & dosage; D010656:Phenylephrine / Q000008:administration & dosage; D015221:Potassium Channels / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014654:Vascular Patency / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D015220:Calcium Channels; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D005996:Nitroglycerin