Original articleContribution 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

- Molsidomine decreases BP in unilaterally 6-OHDA-lesioned rats 10 min after injection.
- Molsidomine jointly with l-DOPA evokes similar decrease in BP in 6-OHDA-lesioned rats.
- The molsidomine-mediated decline in BP was transient and disappeared after 24 h.
- In contrast to molsidomine antihypertensive drugs maintain long-term decline in BP.
- In PD molsidomine may decrease supine hypertension without worsening hypotension.

BackgroundInteraction 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.MethodsThe aim of the present study was to examine the impact of chronic administration of molsidomine (2 mg/kg) and l-DOPA (25 mg/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 24 h after the penultimate and immediately after the last drug doses.ResultsIn 6-OHDA-lesioned rats receiving saline, spontaneous, small decreases in SBP and DBP were observed during the measurements lasting 60 min. Administration of molsidomine alone or in combination with l-DOPA distinctly decreased the BP in 6-OHDA-lesioned rats already after 10 min 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 24 h.ConclusionsOur 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.