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On the mechanism of l ‐DOPA‐induced postural hypotension in the cat

1973; Wiley; Volume: 47; Issue: 3 Linguagem: Inglês

10.1111/j.1476-5381.1973.tb08175.x

1476-5381

K. M. Dhasmana, Bert Spilker,

Obstructive Sleep Apnea Research

Summary The effects of l ‐DOPA on postural hypotension and carotid occlusion pressor effect were studied, mainly in cats the recovery of the blood pressure upon tilting was used as a measure of postural hypotension. l ‐DOPA (30 mg/kg) partially depressed the carotid occlusion pressor effect and caused some degree of postural hypotension, l ‐DOPA (100 mg/kg) had more marked effects the responses returned to control after 90 to 150 minutes. l ‐DOPA itself caused a pressor response in all cats. The dopa decarboxylase inhibitor N 1 ‐( dl ‐seryl)‐ N 2 ‐(2,3,4‐trihydroxybenzyl) hydrazine (RO4‐4602, 50 and 10 mg/kg) had no effect itself on the tilt response but completely prevented the effects of l ‐DOPA on the carotid occlusion pressor effect and postural hypotension. After RO4‐4602 (3 and 1 mg/kg), l ‐DOPA (100 mg/kg) caused a brief rise of blood pressure followed by a longer lasting fall in horizontally‐orientated cats (i.e. ‘supine’ hypotension). No postural hypotension was observed after l ‐DOPA under these conditions. Noradrenaline elicited only small and transient effects on postural hypotension, but dopamine's effects were more marked and longer lasting. Pressor dose‐response relationships for noradrenaline were the same before and after l ‐DOPA, as well as in cats pretreated with l ‐DOPA for 4 days. In cats with kidneys and intestines removed, the tilt reflex was still present. Dose‐response curves to l ‐DOPA were the same as in normal animals. RO4‐4602 (3 mg/kg) prevented postural hypotension and block of the carotid occlusion pressor effect; supine hypotension was also observed after l ‐DOPA. The recovery response to tilting in spinal cats was markedly depressed or absent unless the blood pressure was elevated by angiotensin, in which experiments l ‐DOPA depressed the recovery upon tilting (i.e. induced postural hypotension). Blood pressure responses to tyramine were increased after 10 mg/kg of l ‐DOPA, but depressed after 100 mg/kg. The response to tyramine was not depressed, however, when RO4‐4602 was given to block the dopa‐dopamine conversion. The response to sympathetic stimulation in pithed rats was depressed after l ‐DOPA and dopamine, but not after α‐methyldopa. α‐Methyldopa (300 mg/kg) given acutely caused a moderate degree of postural hypotension and a more marked postural hypotension if given for two days. It is concluded that it is possible to differentiate between the supine and postural hypotension caused by l ‐DOPA and that supine hypotension is due to a central effect and postural hypotension to an extracerebral effect. Postural hypotension is discussed in relation to six hypotheses presented to explain its effect. Postural hypotension after l ‐DOPA is probably not due to α‐adrenoceptor blockade, a central effect or any effect on the kidney. The most likely hypothesis is that l ‐DOPA forms dopamine which acts as a false transmitter in the peripheral sympathetic nervous system.