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Biomedical subjects

L Finch

Publications and source records attributed to L Finch.

At least 55 records · Page 3Linked to original sources
PubMed1975

An increased reactivity in hypertensive rats unaffected by prolonged antihypertensive therapy.

1. Isolated perfused mesenteric arteries obtained from chronic experimental hypertensive rats (deoxycorticosterone/NaCl) exhibited an increased reactivity to noradrenaline, 5-hydroxytryptamine and adenosine 5'-triphosphate (ATP) when compared with similar preparations from age-matched normotensive animals. 2. The dose-response curves to all three vasoconstrictor agents obtained from hypertensive animals exhibited a steeper slope, and higher maximum without any significant change in the threshold dose suggesting that adaptive/structural changes in the blood vessels had taken place. 3. Ten week treatments with antihypertensive combinations of hydrallazine, hydrochlorothiazide and reserpine or hydrallazine and mecamylamine lowered the systolic blood pressures of the hypertensive rats to those of normotensive animals and also reversed secondary changes such as periarteritis nodosa of the mesentery and cardiac hypertrophy. 4. The reactivity of these blood vessels to all these vasoconstrictor agents from the hypertensive rats with a normalized blood pressure was similar to those obtained with untreated hypertensive animals. 5. The persistent increased reactivity in the hypertensive rats after long-term anti-hypertensive treatment suggests that the hyperresponsiveness is secondary to the elevated blood pressures and that the adaptive/structural changes of the blood vessels in chronic hypertensive rats cannot be reversed by prolonged antihypertensive therapy.

Adenosine Triphosphate↗
PubMed1975

Studies on the hypotensive action of alpha-methyldopamine.

1. Intraventricular alpha-methyldopamine (50-200 mug) produced a dose-related fall in blood pressure in conscious spontaneously hypertensive rats. Pretreatment with intraventricular 6-hydroxydopamine prevented this hypotensive effect of alpha-methyldopamine. 2. The hypotensive effect of alpha-methyldopamine was prevented by intraventricular injection of phentolamine or desmethylimipramine, but not by intraperitoneal injection of haloperidol. 3. Pretreatment with U-14,624, a selective central dopamine-beta-hydroxylase inhibitor, prevented the hypotensive effect of alpha-methyldopamine. 4. Alpha-methyldopamine was considerably less potent than noradrenaline as a pressor agent in the pithed rat, but noradrenaline and alpha-methylnoradrenaline were found to be equipotent. 5. Alpha-methyldopamine (1-5 mg i.c.v.) reduced pressor responses elicited by electrical stimulation of the midbrain reticular formation in cats anaesthetized with chloralose. 6. It is concluded that the hypotensive action of alpha-methyldopamine in conscious animals involves intact central alpha-adrenergic neurones and a central adrenergic uptake mechanism for the formation of alpha-methylnoradrenaline.

Animals↗
PubMed1975

Evidence for a central alpha-sympathomimetic action of clonidine in the rat.

The antihypertensive effects of clonidine (0.15 mg kg-1, i.p.) were studied in conscious DOCA/saline hypertensive rats having chronically implanted arterial cannulae. The response to clonidine was markedly reduced by simultaneously administered desipramine (3 mg kg-1, i.p.), antagonized dose-dependently by piperoxan (2-10 mg kg-1, i.v.) and prevented by pretreatment with phentolamine (0.2 mg, i.c.v.). Pretreatment with 6-hydroxydopamine (3 x 250 mu-g, i.c.v.), haloperidol (1 mg kg-1, i.p.), p-chloro-N-methylamphetamine (3.5 mg kg-1, i.p.) or 5,6-dihydroxytryptamine (50 mu-g and 25 mu-g, i.c.v.) did not significantly modify the antihypertensive response. It is concluded that the antihypertensive response to clonidine is mediated via stimulation of central alpha-adrenoceptors and is independent of central dopaminergic receptors and intact central serotoninergic neurons. The necessity for intact central noradrenergic neurons remains uncertain.

Adrenergic alpha-Agonists↗
PubMed1974

The cardiovascular effects of intraventricular clonidine and Bay 1470 in conscious hypertensive cats.

1 Intraventricular administration of clonidine (5-30 mug) and an analogue, BAY 1470 (15-30 mug) to conscious renal hypertensive cats produced a fall in mean blood pressure lasting for approximately 3 hours. This fall in blood pressure was accompanied by a marked bradycardia.2 Pretreatment with intraventricular phentolamine (100-200 mug), piperoxan (40-200 mug) or tolazoline (75-200 mug) abolished the cardiovascular effects of intraventricular clonidine (20 mug).3 The cardiovascular effects of intraventricular clonidine (20 mug) were not modified by the pretreatment with either haloperidol (1 mg/kg i.p.) or desmethylimipramine (1 mg/kg i.p.).4 Emesis was observed 1-2 min after the administration of either clonidine (5-20 mug) or BAY 1470 (30 mug). This preceded the cardiovascular actions and was still seen after pretreatment with haloperidol, desmethylimipramine, phentolamine, piperoxan or tolazoline.5 It is concluded that the centrally mediated cardiovascular responses observed after intraventricular administration of small doses of clonidine are due to stimulation of central alpha-adrenoceptors and are independent of central catecholamine uptake mechanisms and dopamine receptors.

Adrenergic alpha-Antagonists↗
PubMed1973

Rapid recovery of vascular adrenergic nerves in the rat after chemical sympathectomy with 6-hydroxydopamine.

1. Twenty-four hours after the last of 4 intravenous doses of 6-hydroxydopamine (2x50 mg/kg on day 1 and 2x100 mg/kg on day 7) a complete impairment of adrenergic nerve function was observed in various organs of the rat.2. A complete recovery of adrenergic nerve function in vascular smooth muscle was observed 7 days after the last dose of 6-hydroxydopamine whilst in non-vascular smooth muscle recovery took between 14 and 21 days.3. On day 8, noradrenaline depletion produced by 6-hydroxydopamine was not as great in vascular tissues, such as the mesentery and renal artery, as in other tissues, such as the heart and salivary glands. Noradrenaline concentrations recovered much more rapidly in vascular than in other tissues.4. Electron microscope studies of small mesenteric arteries showed a complete destruction of adrenergic nerve terminals 24 h after 6-hydroxydopamine (2x100 mg/kg). However, there was a reappearance of growing terminals within 7 days and after 28 days the regrowth of adrenergic nerve terminals seemed complete.5. From the morphological and functional data it is concluded that 6-hydroxydopamine does produce complete destruction of vascular adrenergic nerve terminals. However, these terminals regenerate more rapidly than those in other tissues. This could explain the failure of intravenously administered 6-hydroxydopamine to prevent the development of experimental hypertension in the rat.

Animals↗
PubMed1973

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

1. alpha-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 alpha-methyldopa, whilst intravenous 6-hydroxydopamine reduced but did not prevent the hypotension.2. The hypotensive effect of alpha-methyldopa was prevented or reversed by intraventricular injection of phentolamine (200 mug/rat).3. Pressor responses obtained by stimulation of the entire sympathetic outflow in the Gillespie & Muir preparation, were unaffected by pretreatment with alpha-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 alpha-methyldopa. Furthermore, alpha-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 alpha-methyldopa. FLA-63, a selective dopamine-beta-hydroxylase inhibitor, prevented the reduction of the pressor responses to hypothalamic stimulation produced by alpha-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 alpha-methyldopa (100 mg/kg i.v.).7. These results strongly suggest that the central actions of alpha-methyldopa are important for its hypotensive effect, although a possible peripheral effect cannot be excluded.

Animals↗