Cardiotoxicity of catecholamines after application of L-DOPA in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR).
In order to estimate the role of the sympatho-adrenal system as a trigger in cardiovascular mortality risk after L-DOPA administration in patients with Parkinsons disease we performed the following experiments in normotensive Wistar-Kyoto-rats (WKY) and spontaneously hypertensive rats (SHR). L-DOPA was given orally in increasing doses (30, 100, 300 mg/kg b.w.). Haemodynamic parameters (BP, HR) were measured by tail cuff plethysmography and catecholamine concentrations in tissues assayed by high pressure liquid chromatography. Stressful situations were induced by experimental myocardial infarction. After administration of L-DOPA a dose-dependent increase in blood pressure in both WKY and SHR was observed with a prolongation in SHR. Significantly increased concentrations of dopamine in the hearts were measured in both strains. Noradrenaline stores in the heart of WKY were more filled than in the heart of SHR. Only in SHR high adrenaline concentration in the adrenal medulla were measured after L-DOPA administration. Circulating adrenaline concentrations were significantly enhanced after myocardial infarction in WKY and could be further elevated by pretreatment with L-DOPA. From the results obtained it is concluded that L-DOPA administration in WKY and SHR leads to exaggerate synthesis and massive release of catecholamines and in consequence to an enhanced cardiovascular mortality risk due to cardiotoxicity of catecholamines. It can be extrapolated that increased cardiovascular mortality risk seen in Parkinson patients treated with L-DOPA and benzerazide is probably associated with increased synthesis and release of catecholamines during stressful situations.
Department of Pharmacology, University of Regensburg, Germany.
M
M
Kammermeier
H F
HF
Grobecker
D000818:Animals; D002395:Catecholamines / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D004298:Dopamine / Q000097:blood / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity*; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D007980:Levodopa / Q000633:toxicity*; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002395:Catecholamines; D015259:Dopamine Agents; D007980:Levodopa; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine