L. Finch

Bio: L. Finch is an academic researcher from Hoffmann-La Roche. The author has contributed to research in topics: Stimulation & Phentolamine. The author has an hindex of 1, co-authored 1 publications receiving 95 citations.

Further evidence for a central hypotensive action of α-methyldopa in both the rat and cat

Abstract: 1. α-Methyldopa (300 mg/kg i.p.) produced a fall in blood pressure in conscious genetic hypertensive rats. Pretreatment with intraventricular 6-hydroxydopamine prevented this hypotensive effect of α-methyldopa, whilst intravenous 6-hydroxydopamine reduced but did not prevent the hypotension. 2. The hypotensive effect of α-methyldopa was prevented or reversed by intraventricular injection of phentolamine (200 μg/rat). 3. Pressor responses obtained by stimulation of the entire sympathetic outflow in the Gillespie & Muir preparation, were unaffected by pretreatment with α-methyldopa (300 mg/kg i.p.). 4. Vasoconstrictor responses to periarterial nerve stimulation of the isolated renal artery preparation of the rat were markedly reduced by pretreatment with α-methyldopa. Furthermore, α-methylnoradrenaline was found to have one-eighth the vasoconstrictor potency of noradrenaline in this particular artery preparation. 5. Pressor responses obtained by stimulation of the posterior hypothalamus or midbrain reticular formation in the rat anaesthetized with urethane were markedly reduced by pretreatment with α-methyldopa. FLA-63, a selective dopamine-β-hydroxylase inhibitor, prevented the reduction of the pressor responses to hypothalamic stimulation produced by α-methyldopa. 6. Stimulation of the posterior hypothalamus in the anaesthetized cat caused both an increase in sympathetic nerve activity and a rise in blood pressure. These responses were markedly reduced 3-4 h after the injection of α-methyldopa (100 mg/kg i.v.). 7. These results strongly suggest that the central actions of α-methyldopa are important for its hypotensive effect, although a possible peripheral effect cannot be excluded.

Centrally induced hypotension and bradycardia after administration of alpha-methylnoradrenaline into the area of the nucleus tractus solitarii of the rat.

Abstract: 1 In anaesthetized rats, bilateral injections of alpha-methylnoradrenaline, noradrenaline or adrenaline into the area of the nucleus tractus solitarii (NTS) of the brain stem caused dose-dependent decreases of systemic arterial blood pressure and heart rate. The effects of alpha-methylnoradrenaline were most pronounced and lasted longest. 2 The cardiovascular effects of alpha-methylnoradrenaline appeared to be restricted to the medio-caudal part of the NTS. 3 Prior administration of the alpha-adrenoceptor blocking agent, phentolamine, reversed the fall in blood pressure and heart rate induced by alpha-methylnoradrenaline into an increase. 4 Systemic administration of atropine combined with vagotomy potentiated the inhibitory effects of alpha-methylnoradrenaline on the cardiovascular system.

Central inhibitory noradrenergic cardiovascular control.

Abstract: Publisher Summary This chapter presents several experiments that indicate that the central hypotensive effect of L-DOPA (L- 3,4-dihydroxyphenylalanin) may be related to an increase of brain stem noradrenaline level. Depletion of brain noradrenaline in neonate or adult rats by intraventricular administration of 6-hydroxydopamine did not affect blood pressure. The hypotensive effect of L-DOPA has also been shown in rats, dogs and cats. Inhibition of extracerebral decarboxylase activity to prevent the peripheral effects of dopamine and noradrenaline, which generate from L-DOPA, is required for the expression of the hypotensive effect of L-DOPA in the rat. A number of experiments were performed to investigate whether low levels of brain noradrenaline would lead to opposite effects. In addition, the chapter also studies the cardiovascular effect of bilateral electrolytic brain stem lesions at the level of the obex in rats anesthetized with ether. Blood pressure in the conscious rats was recorded from a permanent indwelling iliac cannula. Lesioning this area was followed by an acute and severe hypertension.

The hypotensive activity and side effects of methyldopa, clonidine, and guanfacine.

Abstract: Clonidine (Catapres, Catapresan), guanfacine (Estulic), and methyldopa (Aldomet) are the prototypes of centrally acting antihypertensive drugs. Clonidine and guanfacine are lipophilic drugs that readily penetrate into the brain, where they stimulate alpha-adrenergic receptors in the pontomedullary region. The stimulation of these central alpha-adrenergic receptors has been shown to activate an inhibiting neuron, which causes a reduction of peripheral sympathetic tone and a subsequent fall in arterial blood pressure and heart rate. Both a centrally initiated reduction of vagus reflex activity and the activation of presynaptic alpha 2-adrenergic blocking agents in the heart may contribute to the bradycardia. Studies indicate that methyldopa also penetrates into the brain, where it is converted into alpha-methylnorepinephrine. This amine may stimulate the same central alpha-adrenergic receptors as those activated by clonidine, which will result in a hypotensive effect. Possibly, alpha-methyldopamine might also play a role. Accordingly, the modes of action of clonidine and alpha-methyldopa probably are very similar at a basic level. The central adrenergic receptors probably are located postsynaptically. Their receptor demand corresponds more closely to that of the alpha 2-subtype. Central alpha 1-adrenergic receptors might possibly play a part in the modulation of vagally induced baroreflex bradycardia. A discussion on the pharmacological basis of the side effects of the centrally acting antihypertensives has been limited to those adverse reactions that are somehow related to alpha-adrenergic receptors. Sedation, a common side effect, appears to be mediated by central alpha 2-adrenergic receptors, at least in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of clonidine on sleep patterns in man.

Abstract: Clonidine (300 µg orally) increased in man the total duration of sleep and strikingly reduced the duration of REM sleep. Yohimbine (10 mg per os) did not alter the sleep patterns in man but antagonized the effects of clonidine. These results provide evidence that an α sympathomimetic mechanism could suppress REM sleep and increased the total duration of sleep.