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Biomedical subjects

D E Potter

Publications and source records attributed to D E Potter.

At least 73 records · Page 4Linked to original sources
PubMed1985

Does B-HT 920 lower intraocular pressure in cats by interacting with alpha 2- and/or DA2 adrenoceptors?

Topical administration of B-HT 920 (50 micrograms) to the eyes of normal unanesthetized cats produced decreases in intraocular pressure and pupil diameter. The ocular hypotensive effect of B-HT 920 was eliminated by sympathectomy and pretreatment with sulpiride (2 mg/kg, s.c.). B-HT 920 also produced dose-related inhibition of contractions of the cat nictitans elicited by stimulating the pre- and postganglionic sympathetic trunks. B-HT 920-induced suppression of the contracting nictitans was antagonized more effectively by relatively selective DA2 antagonists, sulpiride and domperidone, than by rauwolscine, a relatively selective alpha 2-adrenoceptor antagonist. These data suggest that B-HT 920 produces ocular hypotension in the cat by interacting predominantly with DA2 receptor on peripheral sympathetic nerves.

Adrenergic alpha-Agonists↗
PubMed1985

Forskolin suppresses sympathetic neuron function and causes ocular hypotension.

Recent reports suggest that forskolin can produce ocular hypotension in laboratory animals and man by enhancing formation of cyclic AMP. This proposed mechanism of action implies that forskolin lowers intraocular pressure (IOP) by activating adenylate cyclase at some postjunctional site. Intra-arterial (i.a.) injections of forskolin (10, 33, 100 & 333 micrograms) into the cat nictitating membrane (CNM) preparation produced dose-related inhibition of contractions elicited by electrical stimulation of pre-and postganglionic sympathetic neurons. Interestingly, contractions elicited by i.a. norepinephrine were inhibited less than neuronally mediated contractions. Topically applied forskolin (0.5 mg) to the eyes of unilaterally sympathectomized (SX) rabbits and normal rabbits elicited ocular hypotension in the innervated eyes only. Forskolin (0.5 mg, topically) suppressed the rise in IOP induced by water loading in normal rabbits but was significantly less effective in SX rabbits. These results suggest that forskolin lowered IOP in rabbits and suppressed contraction of the electrically-stimulated CNM, in part, by inhibiting sympathetic neuronal function.

Administration, Topical↗
PubMed1984

Effects of aminotetralins on intraocular pressure and pupillary function in rabbits.

Aminotetralin compounds, A-6, 7-DTN and TL-99, produced bisphasic changes in intraocular pressure (IOP) and pupillary dilatation in rabbits. The rise in IOP appeared to result from an action on extraocular muscles because this effect was not produced by either compound in rabbits with transected extraocular muscles. The ocular hypotensive action of A-6, 7-DTN and TL-99 was markedly attenuated in sympathectomized rabbits indicating that this action resulted from suppression of sympathetic neuronal activity. Inhibition of ocular hypertension induced by waterloading by both compounds and suppression of the IOP recovery rate by A-6, 7-DTN suggested that the latter compound lowered IOP, in part, by inhibiting aqueous humor formation. The ocular hypotensive action of A-6, 7-DTN was antagonized by pretreatment with sulpiride, but not by yohimbine, indicating that dopamine receptors are involved in the response. These studies demonstrated that dopamine agonists can lower IOP and suggest that these types of drugs might prove useful in the therapy of open-angle glaucoma.

Animals↗
PubMed1984

Ocular hypotensive action of ergoline derivatives in rabbits: effects of sympathectomy and domperidone pretreatment.

Ergot derivatives, such as bromocriptine, lergotrile and pergolide, are potent dopaminergic agonists in various biological systems. In topical doses ranging from 0.001 to 1% applied unilaterally, each agent produced dose-related ocular hypotension in normal rabbits. Utilizing an intraocular pressure (IOP) recovery rate method (aqueous formation index), each agent was observed to suppress the recovery rate of IOP in normal rabbits. Pretreatment with a prejunctional dopamine receptor antagonist (domperidone) inhibited the ocular hypotensive effect of bromocriptine and pergolide more than that of lergotrile. In rabbits with unilateral superior cervical ganglionectomies, IOP was lowered appreciably less by these compounds in the denervated eyes. These studies indicate that: a) lowering of IOP by these ergot derivatives is dependent, in part, on suppression of sympathetic neuronal activity; b) the most probable sites of action are DA2 receptors on sympathetic nerve endings or in sympathetic ganglia; c) ocular hypotension is produced, in part, by suppressing aqueous humor formation.

Administration, Topical↗
PubMed1984

Alteration in ocular function induced by phenylethylamine analogs of dopamine.

Dopamine (DA) and three methylated analogs (N-methyldopamine, NMDA; N, N- dimethyldopamine , DMDA ;N,N-di-n- propyldopamine , DPDA) were examined for effects on intraocular pressure (IOP) and pupil diameter (PD) in normal rabbits, sympathectomized (SX) rabbits and rabbits with transected extraocular muscles ( EOMX ) following topical administration. In normal rabbits, the predominant effect of DA, NMDA and DMDA was transient, unilateral ocular hypertension with minimal effects on PD. In contrast, DPDA produced bilateral ocular hypotension in normal rabbits. DA and NMDA did not produced ocular hypertension in EOMX rabbits indicative of an involvement of extraocular muscles in normal rabbits. In SX rabbits, NMDA produced mydriasis and exaggerated ocular hypertension followed by significant ocular hypotension; the ocular hypotensive phase was antagonized by timolol pretreatment. The ocular hypotensive activity of DPDA seen in normal rabbits was absent in SX rabbits suggestive of a neuronal site of action for DPDA. DPDA inhibited contraction of the cat nictitating membrane elicited by stimulation of pre- and postganglionic sympathetic nerves. This effect was antagonized by a dopamine (DA2) antagonist metoclopramide, indicative of a prejunctional site of action. NMDA and DA suppressed ocular hypertension induced by water loading. Only NMDA depressed the IOP recovery rate in response to infusion of hypertonic saline indicating suppression of aqueous humor formation. These results suggest that DA, NMDA and DMDA produce an initial ocular hypertension by contracting extraocular muscles. Timolol antagonized the ocular hypotensive effect of NMDA in SX rabbits indicating that this response is, in part, a function of beta-adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

An in vivo model for dissociating alpha 2-and DA2-adrenoceptor activity in an ocular adnexa: utility of the cat nictitating membrane preparation.

Recent reports from this laboratory indicate that dopamine (DA2) agonists can lower intraocular pressure (IOP) in rabbits, monkeys and rats. This communication suggests that the cat nictitating membrane (CNM) preparation is a useful model for localizing the site(s) and mechanism(s) of action of dopamine (DA2) agonists and that this model can be used to discriminate between alpha 2 and DA2 activity. This in vivo preparation consists of indirect (neuronal)- and direct (agonist)-induced activation of the CNM by: 1) pre- and postganglionic stimulation of sympathetic nerves and 2) injection of norepinephrine (NEPI) into the external carotid artery (i.a.). A variety of DA2-agonists (ergolines, azepines, aminotetralins, aporphines) can cause dose-dependent depression of neuronally mediated contractions with minimal effects on contractions elicited by NEPI i.a. Characteristically, DA2-agonists depressed contractions elicited by low frequency (2 & 4 Hz) stimulation more than high frequency (6 & 8 Hz) stimulation. For example, the inhibitory effects of an ergoline derivative LY141865 on neuronally mediated contractions of the CNM could be reversed (or prevented) by relatively selective DA2 antagonists, such as sulpiride and domperidone, but not by relatively selective alpha 2-antagonists, such as yohimbine and rauwolscine. Interestingly, alpha 2-adrenoceptor agonists, such as clonidine and xylazine, caused less depression of nerve-stimulated responses than did DA2-agonists at the same dose. This modest suppression by alpha 2-agonists could be inhibited by yohimbine but not by sulpiride or domperidone. These results with the CNM document the presence of DA2 receptors on sympathetic neurons innervating an ocular adnexa and demonstrate a model for dissociating DA2 from alpha 2 activity.

Adrenergic alpha-Agonists↗
PubMed1983

Severe hypertension in children with renal disease: treatment with minoxidil.

Sixteen children with renal disease and severe hypertension refractory to other drugs were treated with minoxidil for periods of five days to 77 months. The maximum dose ranged from 0.05 to 1.88 mg/kg/d. With therapy, the mean BP decreased from 158/112 to 133/90. Thirteen children had an antihypertensive response. 2 had progressive rejection of transplanted kidneys, and 1 received a low dose and failed to respond. Complications were hypertrichosis in 14; fluid retention in 4, with congestive heart failure in 1; and decreased renal function in 2. Pericarditis, possibly related to minoxidil, occurred in one child. Minoxidil is a valuable antihypertensive drug in children but should be used with caution.

Adolescent↗
PubMed1982

Effects of ethanol, acetaldehyde and acetate on insulin release from perifused pancreatic islets.

It has been postulated that ethanol-induced changes in carbohydrate hemeostasis are mediated in part by alterations in pancreatic endocrine function. In this study ethanol (40, 120 and 240 mg/dl) produced dose-related suppression of immunoreactive insulin (IRI) release from isolated rat islets perifused with glucose and theophylline. Acetaldehyde inhibited IRI release at a concentration (39 mg/dl) much higher than can be achieved in vivo. A high concentration (29 mg/dl) of acetate did not influence IRI release. These results suggest that the ability of ethanol to inhibit IRI release resides principally in the parent compound and not its metabolites.

Acetaldehyde↗
PubMed1981

Acid-base changes and acetate metabolism during routine and high-efficiency hemodialysis in children.

Changes in acid-base status and plasma acetate concentrations were studied in eight children during 11 hemodialysis sessions. During dialysis, the blood bicarbonate concentration fell (20.5 +/- 0.7 to 19.6 +/- 0.8 mEq/liter), the Pco2 fell (33.4 +/- 0.8 to 27.5 +/- 1.4 mm Hg), and the pH rose (7.42 +/- 0.01 to 7.48 +/- 0.02). During the hour after dialysis, the bicarbonate concentration rose to normal (23.4 +/- 0.7 mEq/liter), the PCO2 rose (32.8 +/- 0.8 mm Hg), and the pH remained unchanged. The half-life of plasma acetate, measured after dialysis, was 8.7 min. During five "high-efficiency" dialysis sessions (urea clearance, greater than 3.0 ml/min/kg), blood bicarbonate concentration fell 3.2 mEq/liter, PCO2 fell 8.7 mm Hg, and plasma acetate rose to 7.51 mmoles/liter, whereas during six "routine efficiency" dialysis sessions (urea clearance. 1.5 to 3.0 ml/min/kg), blood bicarbonate rose 1.0 mEq/liter, PCO2 fell 36 mm Hg, and plasma acetate rose to 3.52 mmoles/liter. At 1 hour after the end of dialysis, blood bicarbonate, PCO2, and plasma acetate concentrations were similar in the two groups. Clinical problems occurred more frequently in the high-efficiency group during dialysis although the difference was not significant. The data indicate that (1) dialysis with acetate buffer effectively corrects predialysis metabolic acidosis, (2) although children have a high rate of acetate metabolism, during high-efficiency dialysis this rate is exceeded by the influx of acetate, and acid-base abnormalities occur. These abnormalities are transient but may cause clinical problems.

Acetates↗
PubMed1981

Circadian rhythm in intraocular pressure: a rabbit model.

An animal model for study of the circadian rhythm in intraocular pressure (IOP) was developed using carefully maintained environmental lighting conditions. Highly predictable, precipitous increases and decreases in IOP of somewhat more than 10 mm Hg were found to be closely correlated with the onset of darkness and light, respectively. The daily spontaneous variations in IOP, once entrained, were maintained in constant darkness, but were eliminated by constant light, as is similarly seen in many mammalian systems. This model provides a novel means of investigating circadian IOP oscillation, which has been shown to be especially amplified in primary open angle glaucoma (POAG). This new rabbit model may also warrant consideration for use in screening ocular antihypertensive drugs since it could obviate the gross physiological manipulations and concomitant side effects inherent in the popular methods of inducing ocular hypertension in animal models.

Animals↗
PubMed1981

Steric structure activity relationships of various adrenergic agonists: ocular and systemic effects.

Dextrorotatory (d) forms of adrenergic drugs are known to be much less active than the levo (l) forms in effecting classical adrenergically mediated responses (alpha, beta 1, beta 2) in metabolic organs and cardiovascular tissues. Adrenoceptor intrinsic activity and affinity, enzymatic inactivation and neuronal uptake are all known to be relatively selective for the l-forms. It is known, however, that the d-isomers of certain agonists, such as isoproterenol, are as effective or even more effective ocular hypotensive agents than their respective l-forms or the racemates (dl) in rabbits. We tested the d- and l-isomers of epinephrine (alpha, beta 1, beta 2), norepinephrine (alpha, beta 1), phenylephrine (alpha 1), isoproterenol (beta 1, beta 2) and soterenol (alpha, beta 2) for their comparative effects after topical administration on intraocular pressure (IOP), pupil diameter (PD), arterial blood pressure (ABP) (after both topical and i.v. administration), aqueous cAMP, and aqueous and plasma lactate and glucose in the normotensive rabbit model. The results with ABP and concomitant changes in plasma biochemical correlates normally associated with adrenergic mechanisms were consistent with well established theory of stereospecificity. Data from ocular parameters, however, suggest that d-isomers of adrenergic agents evoke ocular responses that are divergent from this theory. The relation of ocular and systemic pressure responses with their respective biochemical correlates suggests that some d-isomers of adrenergic stimulants may be acting as partial agonists.

Adrenergic beta-Agonists↗
PubMed1980

The effects of topical prazosin on normal and elevated intraocular pressure and blood pressure in rabbits.

A 0.1 mg (base) dose of prazosin, a postsynaptic alpha- (alpha 1) adrenoceptor antagonist, in rabbits effected an early decrease in arterial blood pressure, normal intraocular pressure (IOP) and IOP artificially elevated by water loading. The late drug effects suppressed elevated IOP, but not normal IOP. The IOP effects of prazosin seem largely independent of the effect on blood pressure.

Administration, Topical↗