title: Contribution of the nitric oxide donor molsidomine and the antiparkinsonian drug l-DOPA to the modulation of the blood pressure in unilaterally 6-OHDA-lesioned rats.
abstract: BACKGROUND
  Interaction between dopaminergic and nitrergic neurotransmission in the brain plays a crucial role in the control of motor function and in the regulation of blood pressure (BP). In Parkinson's disease (PD), dopaminergic denervation of the striatum leads to disturbances in the nitrergic system in the basal ganglia. Recently, it has been demonstrated that addition of a low dose of the nitric oxide donor molsidomine to l-DOPA therapy improves dopaminergic neurotransmission in the denervated nigrostriatal system and weakens dyskinesias in rodent models of the disease.
  
  
  METHODS
  The aim of the present study was to examine the impact of chronic administration of molsidomine (2mg/kg) and l-DOPA (25mg/kg), alone and in combination, on systolic (SBP) and diastolic (DBP) blood pressure in the anesthetized, unilaterally 6-OHDA-lesioned rats. The measurement of SBP and DBP was performed 24h after the penultimate and immediately after the last drug doses.
  
  
  RESULTS
  In 6-OHDA-lesioned rats receiving saline, spontaneous, small decreases in SBP and DBP were observed during the measurements lasting 60min. Administration of molsidomine alone or in combination with l-DOPA distinctly decreased the BP in 6-OHDA-lesioned rats already after 10min compared to those treated with saline or l-DOPA alone, respectively. In both groups, the molsidomine-mediated declines in BP persisted till the end of measurement but they disappeared after 24h.
  
  
  CONCLUSIONS
  Our results indicate that in this PD model molsidomine evokes a short-lasting decrease in BP in contrast to conventional antihypertensive drugs that maintain long-term effect and worsen orthostatic hypotension in parkinsonian patients.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neuro-Psychopharmacology, 31-343 Kraków, Smętna street 12, Poland. Electronic address: lorenc@if-pan.krakow.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Lorenc-Koci
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neuro-Psychopharmacology, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Czarnecka
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neuro-Psychopharmacology, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Kamińska
authors.affiliation: Jagiellonian University Medical College, Department of Pharmacological Screening, Chair of Pharmacodynamic, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Knutelska
authors.affiliation: Jagiellonian University Medical College, Department of Pharmacological Screening, Chair of Pharmacodynamic, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Jagiellonian University Medical College, Department of Pharmacological Screening, Chair of Pharmacodynamic, Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dudek
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage*; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000978:Antiparkinson Agents; D020030:Nitric Oxide Donors; D007980:Levodopa; D016627:Oxidopamine; D008981:Molsidomine
keywords: Diastolic blood pressure; Molsidomine; Parkinson’s disease; Systolic blood pressure; l-DOPA