Biomedical subjects

M C Koss

Publications and source records attributed to M C Koss.

At least 37 records · Page 2Linked to original sources

PubMed1994

Histamine H3 receptor activation inhibits sympathetic-cholinergic responses in cats.

Experiments were undertaken to determine the effect of the selective histamine H3 receptor agonist (R)-alpha-methylhistamine on the amplitude of neurally evoked electrodermal (sudomotor) responses in anesthetized cats. (R)-alpha-Methylhistamine produced comparable dose-related depressions of these evoked sympathetic-cholinergic electrodermal responses elicited by either pre- or postganglionic nerve stimulation. Responses evoked by i.a. methacholine were not depressed by pretreatment with (R)-alpha-methylhistamine. (R)-alpha-Methylhistamine inhibition of preganglionic evoked responses was antagonized by pretreatment with the histamine H3 receptor antagonist thioperamide, but not by pretreatment with selective blockers of histamine H1 or histamine H2 receptors (chlorpheniramine or cimetidine). Pretreatment with thioperamide did not antagonize presynaptic inhibition produced by i.v. (-)-epinephrine, nor did rauwolscine block the inhibition produced by (R)-alpha-methylhistamine. These results suggest that (R)-alpha-methylhistamine stimulates presynaptic histamine H3 receptors located on sudomotor postganglionic nerve endings to depress neurally evoked release of acetylcholine. (R)-alpha-Methylhistamine does not appear to act at an autonomic ganglionic site in this system.

Animals↗

PubMed1994

Adrenoceptor mechanisms in epinephrine-induced anterior choroidal vasoconstriction in cats.

These studies were undertaken to determine the role of epinephrine in the anterior choroidal circulation and to define the relative contribution of adrenoceptor subtypes in this response. Intra-arterial administration of l-epinephrine (0.03-1 microgram) produced vasoconstrictor responses in the anterior choroid of anesthetized cats as measured using laser-Doppler flowmetry. Ipsilateral nictitating membrane contractions were simultaneously recorded. Responses of both organs were blocked by intravenous treatment with the non-selective alpha-adrenoceptor antagonist phentolamine; however, only nictitating membrane contractions were significantly antagonized with the selective alpha 1-adrenoceptor antagonist, prazosin. In contrast, alpha 2-adrenoceptor blockade with rauwolscine had no depressant effect on the nictitating membrane but was a potent antagonist for epinephrine-induced ocular vasoconstriction. This differential ocular receptor type activation was confirmed with the use of more selective alpha-adrenoceptor agonists. Both the alpha 1-adrenoceptor agonist, methoxamine, and the selective alpha 2-adrenoceptor stimulant, B-HT 933, produced choroidal vasoconstriction when given intra-arterially. B-HT 933 was as potent as methoxamine in producing choroidal vasoconstriction which suggests a high ratio of alpha 2-adrenoceptors in this vascular bed. B-HT 933 was much less potent than methoxamine in producing contraction of the nictitating membrane. These results demonstrate the usefulness of laser-Doppler flowmetry in studies of the choroidal circulation and suggest that, unlike the nictitating membrane, epinephrine-induced anterior segment vasoconstriction is mediated by both postjunctional alpha 1- and alpha 2-adrenoceptors with alpha 2-adrenoceptors being predominant.

Adrenergic alpha-Agonists↗

PubMed1994

Ocular effects of alpha 2-adrenoceptor activation in anesthetized cats.

The present study was undertaken to determine the effects of direct administration of the selective alpha 2-adrenoceptor stimulant, B-HT 933, on choroidal blood flow, intraocular pressure and pupil size in anesthetized cats. Anterior segment choroidal blood flow was measured using laser-Doppler flowmetry. B-HT 933 administered by intra-arterial, topical and intracameral routes produced a significant depression of ocular blood flow which was largely abolished by pretreatment with rauwolscine. B-HT 933 did not lower IOP in any of these preparations. The largest doses of B-HT 933 caused a modest mydriasis when given intracamerally. However, this pupillary dilation was not blocked by rauwolscine. These results demonstrate that alpha 2-adrenoceptor activation can produce pronounced depression of anterior segment choroidal blood flow but does not cause a concomitant lowering of IOP or mydriasis in anesthetized cats.

Adrenergic alpha-Agonists↗

PubMed1993

Adrenoceptor subtypes involved in neurally evoked sympathetic vasoconstriction in the anterior choroid of cats.

Electrical stimulation of the preganglionic cervical sympathetic nerve produced ocular vasoconstrictor responses as measured from the anterior choroid of anesthetized cats using laser-Doppler flowmetry. Ipsilateral nictitating membrane contractions were simultaneously measured as an established index of neural sympathetic activation. The frequency-response relationships for both effectors were nearly linear from 0.125-32 Hz. When elicited at 2-min intervals, submaximal evoked responses of both systems were stable for more than 1 hr. Ocular vasoconstrictor and nictitating membrane responses were blocked in a dose-dependent fashion by intravenous treatment with the non-selective alpha-adrenoceptor antagonist phentolamine (0.1-3.0 mg kg-1) and with phenoxybenzamine (3.0 mg kg-1) as well as with the selective alpha 1-adrenoceptor antagonist, prazosin (10-300 micrograms kg-1). In contrast, neither evoked response was antagonized by alpha 2-adrenoceptor blocker, yohimbine (10-300 micrograms kg-1), nor with rauwolscine (500 micrograms kg-1). No significant alteration in magnitude of ocular vasoconstriction was seen with blockade of either muscarinic (atropine, 1 mg kg-1) or beta-adrenergic (propranolol, 1 mg kg-1) receptors. These results demonstrate the usefulness of laser-Doppler flowmetry in studies of the choroidal circulation and suggest that, as previously established for the nictitating membrane, adrenergic neurogenic vasoconstriction in the anterior segment of the eye is mediated almost exclusively by alpha 1-adrenoceptor mechanisms.

Animals↗

PubMed1993

Prejunctional inhibition of sympathetically evoked pupillary dilation in cats by activation of histamine H3 receptors.

Frequency-dependent pupillary dilations were evoked by electrical stimulation of the pre- or post-ganglionic cervical sympathetic nerve (sympatho-excitation) or the hypothalamus (parasympatho-inhibition) in sympathectomized anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist (R)-alpha-methylhistamine (R alpha MeHA) produced a dose-dependent depression of mydriasis due to direct neural sympathetic activation but had no effect on responses elicited by parasympathetic withdrawal. The histamine H2 receptor agonist, dimaprit, was inactive. R alpha MeHA was much more effective in depressing sympathetic responses obtained at lower frequencies when compared to higher frequencies of stimulation. Responses evoked both pre- and postganglionically were inhibited by R alpha MeHA. This peripheral sympatho-inhibitory action of R alpha MeHA was antagonized by the histamine H3 receptor blocker thioperamide but not by intravenous pretreatment with the histamine H1 receptor antagonist chlorpheniramine. Histamine H2 receptor blockers cimetidine and ranitidine were also without effect. R alpha MeHA did not depress pupillary responses elicited by i.v. (-)-adrenaline. The results demonstrate that histamine H3 receptors modulate sympathetic activation of the iris at a site proximal to the iris dilator muscle. The predominant mechanism of action appears to the prejunctional inhibition of noradrenaline release from postganglionic sympathetic nerve endings. However, a concomitant ganglionic inhibitory action cannot be excluded.

Animals↗

PubMed1993

Can the 5-HT2/1c agonist DOI cause differential sympatho-excitation in nerves supplying the heart in anaesthetized cats?

A comparison of the effects on sympathetic nerve activity to the heart of intravenous administration of the selective 5-HT2/1c agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) alone and in the presence of the peripherally acting 5-HT2/1c antagonist BW501C67 were made in alpha-chloralose anaesthetized cats. Activity in both cardiac sympathetic nerves running in the vagus and in both inferior cardiac nerves was simultaneously recorded. In addition renal and phrenic nerve activity, heart rate, arterial blood pressure, femoral arterial flow and tracheal pressure were also recorded. DOI evoked a rise in blood pressure and increased femoral arterial resistance in both groups of animals. In the BW501C67 pretreated animals, DOI had no effect on heart rate but caused a significant increase in all sympathetic nerve activities. In non-pretreated animals, however, the rise in blood pressure was associated with variable effects on sympathetic nerve activity, a significant rise only occurring in renal nerve activity. In these experiments DOI evoked a bradycardia. The variability in sympathetic nerve activity in the non-pretreated animals may have resulted from the rise in blood pressure evoking a baroreceptor-mediated central sympathoinhibition which would interfere with the central sympathoexcitatory effects of DOI. It is concluded that centrally, DOI will cause sympathoexcitation. In addition, intravenous DOI acting on 5-HT2 receptors on bronchial smooth muscle evokes bronchoconstriction as indicated by the very large rise in tracheal pressure in non-BW501C67-pretreated animals. If not controlled this severely compromises respiration leading to a large overestimate of the sympathoexcitatory effects of stimulation of central 5-HT2/1c receptors.

Amidines↗

PubMed1993

Distribution of neurally activated postjunctional adrenoceptors in cat forelimb vasculature.

We assessed the relative contribution of postjunctional alpha-adrenoceptor subtypes in neurally evoked vasoconstrictor responses in the forelimb of anesthetized cats. Preganglionic stimulation of the thoracic sympathetic nerve trunk produced frequency-related decreases in blood flow of the entire forelimb as measured by ultrasonic flowmetry as well as vasoconstriction in the digital cutaneous bed as measured by laser-Doppler flowmetry. Vasoconstrictor responses were not altered significantly by intravenous (i.v.) treatment with propranolol (1 mg/kg) or atropine (1 mg/kg). In the entire limb, prazosin, (3-100 micrograms/kg i.v.) was a more potent antagonist of neurally evoked responses as compared with rauwolscine. In contrast, rauwolscine (10-300 micrograms/kg i.v.) was a more effective antagonist in the cutaneous bed. Combined treatment with both prazosin and rauwolscine was far more effective than either antagonist given alone in blocking vasoconstriction regardless of the measurement site. Moreover, basal cutaneous blood flow was increased by rauwolscine but not by prazosin. These results suggest that both subtypes of postsynaptic alpha-adrenoceptors are activated by sympathetic nerve stimulation. In the cutaneous bed, alpha 2-adrenoceptors appear to predominate. In addition, cutaneous vascular tone also appears to be regulated by hormonal alpha 2-adrenoceptor activation in cats.

Adrenergic alpha-Antagonists↗

PubMed1993

Postjunctional alpha 1- and alpha 2-adrenoceptors in cat forepaw vasculature.

Preganglionic stimulation of the thoracic sympathetic nerve trunk produced frequency-related decreases of ulnar arterial blood flow in the forepaw of anesthetized cats as measured by ultrasonic flowmetry. Vasoconstrictor responses were not altered by administration of propranolol or atropine. When given alone, both prazosin (3-100 micrograms/kg, i.v.) and rauwolscine (10-300 micrograms/kg, i.v.) produced only a modest reduction of sympathetic evoked vasoconstriction. However, extensive blockade was obtained when both antagonists were administered to the same animal. These results suggest that both alpha 1- and alpha 2-adrenoceptors coexist at postsynaptic sites in the vasculature of the cat paw and that neural activation of either type results in potent vasoconstriction.

Animals↗

PubMed1992

Comparison of peripheral and central nervous system sympatholytic actions of prazosin using the cat nictitating membrane.

Prazosin is a highly selective alpha 1-adrenoceptor antagonist that decreases blood pressure by actions on both the peripheral and central (CNS) divisions of the nervous system. The present investigation was undertaken in an attempt to characterize the relative contribution of these two sympatholytic sites of action. Submaximal contractions of the nictitating membranes were evoked by electrical stimulation of the preganglionic cervical sympathetic nerve trunk and by stimulation of the posterior hypothalamus in anesthetized cats. In initial control experiments, phenoxybenzamine (0.1-3.0 mg/kg i.v.) produced an equivalent depression of evoked nictitating membrane responses from both peripheral and CNS sites of activation which suggests only a peripheral blocking action as well as functional equivalence of the intensity of CNS and peripheral nerve stimulation. In contrast, prazosin (3-300 micrograms/kg i.v.) caused a differential dose-related depression of the evoked responses with ED50s of 81.5 micrograms/kg (peripheral stimulation) and 12.5 micrograms/kg (CNS stimulation) respectively; P less than 0.05. Pretreatment with rauwolscine (500 micrograms/kg i.v.) totally prevented the differential CNS sympatho-inhibition produced by prazosin. These results indicate that, although both CNS and peripheral sites of drug action are manifest, the ED50 for prazosin-induced CNS sympatho-inhibition is approximately 6-fold less than that required for direct alpha 1-adrenoceptor blockade at the end organ. In addition, prazosin produces CNS sympatho-inhibition indirectly by means of an alpha 2-adrenoceptor mechanism.

Anesthesia↗

PubMed1992

Activation of histamine H3 receptors produces presynaptic inhibition of neurally evoked cat nictitating membrane responses in vivo.

This study was undertaken in order to determine the potential role of prejunctional histamine H3 receptors in an in vivo adrenergic model system. Frequency-dependent nictitating membrane responses were elicited by sympathetic nerve stimulation in anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist, (R)-alpha-methylhistamine (R alpha MeHA) produced a dose-related depression of amplitude of the evoked nictitating membrane responses with a threshold of about 10 micrograms/kg and maximal effect (50% depression at the lowest frequency; 0.5 Hz) seen at 100-300 micrograms/kg. Responses obtained with low frequency stimulation were more sensitive to depression by R alpha MeHA than were responses evoked with higher frequencies of stimulation. Larger doses of R alpha MeHA given to the same animals, failed to produce additional inhibition. R alpha MeHA depressed the amplitude of nictitating membrane responses evoked by either pre- or postganglionic nerve stimulation to an equivalent degree. This depressant action of R alpha MeHA was antagonized by pretreatment with the specific histamine H3 antagonist, thioperamide (3 mg/kg), but not by combined pretreatment with histamine H1 and H2 blockers chlorpheniramine (300 micrograms/kg) and cimetidine (5 mg/kg). Intravenous administration of adrenaline (1-30 micrograms/kg) also produced graded nictitating membrane responses that were not altered by subsequent administration of R alpha MeHA. These results suggest that histamine H3 receptors are involved in the modulation of neurally evoked noradrenaline release in the cat nictitating membrane by an inhibitory presynaptic action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Neurogenic cutaneous vasodilation in the cat forepaw.

The present experiments were undertaken to determine, using Laser Doppler flowmetry, if elimination of efferent constrictor mechanisms would unmask cutaneous vasodilator responses following preganglionic sympathetic nerve stimulation in the forepaw of anesthetized cats. We also addressed the question of a potential causal relationship between neurally evoked vasodilator and sudomotor responses. Three separate anti-adrenergic regimens were utilized: (1) acute guanethidine administration (1-2 mg/kg); (2) chronic monoamine depletion with reserpine (5 mg/kg) and alpha-methyl-para-tyrosine (2 x 300 mg/kg); and (3) alpha-adrenoceptor blockade with prazosin (300 micrograms/kg) and yohimbine (0.5 mg/kg). Guanethidine treatment produced a significant depression of basal cutaneous blood flow whereas alpha-adrenoceptor blockade did not. In all three groups, stimulation of the preganglionic thoracic sympathetic nerve trunk produced intensity-dependent increases of digital skin blood flow along with near-maximal sympathetic-cholinergic sudomotor (electrodermal) responses recorded simultaneously from the same paw. Vasodilator responses were not altered by intravenous propranolol (1 mg/kg) or atropine (1 mg/kg); however, evoked sudomotor responses were totally blocked by atropine. Low doses (1.5 mg/kg i.v.) of hexamethonium selectively abolished the cutaneous vasodilator responses but not concomitantly evoked sudomotor responses. These results demonstrate, using direct measurements of blood flow, that cutaneous digital vasodilation can be measured in cats following removal of vasoconstrictor mechanisms either pre- or postjunctionally. Neither muscarinic nor beta-adrenoceptor mechanisms appear to be involved. These experiments also suggest that cutaneous vasodilation is not a consequence of concomitant sudomotor activation.

Adrenergic alpha-Antagonists↗

PubMed1991

Mechanism of ketanserin-induced sympatho-inhibition.

Experiments were undertaken to determine if sympatho-inhibition produced by ketanserin is due to antagonism of central nervous system alpha 1-adrenoceptors rather than central 5-HT2 receptors and if (like prazosin) it produces sympatho-inhibition indirectly via a central (presynaptic) alpha 2-adrenoceptor mechanism. Administration of ketanserin (0.03-3.0 mg/kg i.v.) caused a dose-related depression of sympathetic-cholinergic electrodermal responses evoked by electrical stimulation of the hypothalamus in pentobarbital anesthetized cats. No effect of ketanserin was observed on electrodermal responses evoked by preganglionic sympathetic nerve stimulation nor did the more specific 5-HT2 receptor antagonist, cinanserin, produce a central sympatholytic effect at dosages up to 3 mg/kg i.v. Pretreatment with alpha 2-adrenoceptor blockers yohimbine, idazoxan, or rauwolscine significantly antagonized ketanserin-induced sympatho-inhibition. Depletion of central nervous system (CNS) monoamines totally prevented ketanserin-induced sympatho-inhibition although clonidine (30 micrograms/kg i.v.) continued to be effective. These results suggest that ketanserin acts in the CNS to reduce sympathetic reactivity by blocking alpha 1-adrenoceptors and not 5-HT2 receptors. In this regard, ketanserin appears to act in a manner similar to other alpha 1-adrenoceptor antagonists (e.g. prazosin and indoramin) by an apparent presynaptic facilitation of alpha 2-adrenoceptor mediated tonic inhibition descending from the lower brainstem.

Adrenergic alpha-Antagonists↗

PubMed1991

Choroidal and ciliary body blood flow analysis: application of laser Doppler flowmetry in experimental animals.

Laser Doppler flowmetry (LDF) measures the flux of red blood cells in a vascular network embedded in tissue. In the present report, choroidal and ciliary body blood flow was measured continuously using an LDF technique in pentobarbital anesthetized cats. Blood flow measurements were made from the choroid beneath the lateral and superior rectus muscles and from the surface above the ciliary body 2-3 mm posterior to the limbus. In some experiments, the sympathetic nerve to the eye was stimulated; in others, intraocular pressure (IOP) was monitored manometrically with a controlled saline infusion delivered into the anterior chamber to gradually elevate IOP. Norepinephrine (NE) and methacholine (MC) also were tested for their effects on choroidal blood flow when given intravenously and intra-arterially. Transient bilateral carotid artery occlusions produced a significant drop in blood flow, but flow did not decrease to zero probably due to collateral contribution of the vertebral circulation. Sympathetic nerve stimulation produced a frequency-dependent decrease in both choroidal and ciliary body blood flow with the latter exhibiting a lower threshold and a greater magnitude of effect. Gradual elevation of IOP produced a proportional decrease in choroidal blood flow. The level of intraocular pressure required to decrease blood flow was dependent on the existing ocular perfusion pressure. Both intravenous and intra-arterially administered NE produced dose-dependent decreases of choroidal blood flow despite graded increases of systemic arterial blood pressure. In contrast, MC produced dose-dependent increases of choroidal blood flow in conjunction with graded decreases of systemic blood pressure. The results of the present report demonstrate the validity of the LDF technique for performing continuous reading of blood flow changes in the choroid and ciliary body of experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Neural activation of alpha-2 adrenoceptors in cat cutaneous vasculature.

The present study was designed to assess the relative contribution of postjunctional alpha-1 and alpha-2 adrenoceptors in neurally evoked cutaneous vasoconstrictor responses in anesthetized cats. Preganglionic stimulation of the thoracic sympathetic nerve trunk produced an intensity-related decrease of digital skin blood flow as measured by laser-Doppler flowmetry. Sympathetic-cholinergic sudomotor (electrodermal) responses were recorded simultaneously as an additional index of neuronal activation. Vasoconstrictor responses were not altered by pretreatment with i.v. propranolol (1 mg/kg) or atropine (1 mg/kg) and were refractory to low doses (2 mg/kg) of hexamethonium. As expected, atropine abolished evoked skin potential responses which were also sensitive only to higher doses (20 mg/kg) of hexamethonium. Pretreatment with either phentolamine (1 mg/kg i.v.), yohimbine (0.5 mg/kg i.v.) or prazosin (0.3 mg/kg i.v.) produced significant reduction of sympathetic vasoconstriction with blockade by phentolamine and yohimbine being far greater than that seen with prazosin. In animals previously given prazosin (0.3 mg/kg), subsequent administration of yohimbine (0.5 mg/kg) almost totally blocked the remaining evoked cutaneous vasoconstriction. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors are present in the cutaneous bed of the cat with the predominant effect mediated by innervated alpha-2 adrenoceptors.

Animals↗

PubMed1990

Effect of prazosin on spontaneous sympathetic-cholinergic activity.

Tonic sympathetic-cholinergic electrodermal (sudomotor) activity was measured in intact anesthetized and unanesthetized decerebrate and decerebrate-spinalized cats. Prazosin (3-100 micrograms/kg i.v.) depressed spontaneous electrodermal activity in intact anesthetized cats in a dose-dependent fashion (ED50 4.8 micrograms/kg). Prazosin's action was almost totally abolished by monoamine depletion with reserpine and a synthesis inhibitor. The alpha 2-adrenoceptor blocker, yohimbine (0.5 mg/kg i.v.) also antagonized prazosin-induced sympatho-inhibition. Prazosin reduced tonic sudomotor activity in unanesthetized decerebrate cats in a dose-dependent fashion (ED50 5.5 micrograms/kg i.v.) but was without effect in spinalized preparations. These results support the hypothesis that, in this system, prazosin produces sympatho-inhibition indirectly by means of an alpha 2-adrenoceptor-mediated mechanism, an effect which appears to be prejunctional. It is proposed that prazosin acts at the level of the spinal cord to facilitate ongoing alpha 2-adrenergic inhibition arising from supra-spinal loci.

Animals↗

PubMed1990

Parasympathetic nervous control of intraocular pressure.

Electrical or chemical activation of the oculomotor nucleus (ONC) was performed in pentobarbital anesthetized cats to determine the role of parasympathetic nervous input to the eye in modulating intraocular pressure (IOP). In all animals, the vagosympathetic nerve trunks were sectioned bilaterally at the mid-cervical level. Intracranial stimulation of the ONC produced miosis and a bilateral sustained rise in IOP with little or no cardiovascular response. During stimulation, IOP increased by approximately 35-40%, with an additional small rise seen when the current was turned off. The secondary rise in IOP probably represents the actual pressure level reached which was otherwise masked by intense accommodation due to stimulation. The rise in IOP was not antagonized with gallamine triethiodide. However, both IOP and pupillary responses were blocked by either hexamethonium (1.5 mg kg-1, i.v.) or atropine (0.5 mg kg-1, i.v.). These results provide evidence for a neural parasympathetic mechanism for increasing IOP in cats. In another group, activation of ONC following electrolytic lesion of the preganglionic parasympathetic nerve to one eye, produced a rise in IOP and miosis only on the side with intact oculomotor nerve indicating that the rise in IOP is in part mediated by nerve fibers that travel to the eye along the oculomotor nerve trunk. Microinjection of L-glutamate (2.5 x 10(-7) M) into the ONC produced a bilateral rise in IOP that lasted for more than 15 min. This increase in IOP was greater than 50% of control levels and was accompanied with miosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Ocular effects of dipivalyl esters of epinephrine and alpha-methylepinephrine.

The intraocular pressure (IOP) and pupillary effects of dipivalyl esters of epinephrine and alpha-methylepinephrine were compared after topical application in conscious rabbits. Both dipivalyl-alpha-methylepinephrine (DP alpha meE) and dipivalylepinephrine (DPE) produced a dose-dependent pupillary dilation (PD) and decrease in IOP. The onset of PD was approximately 30 min for both agents and reached maximal plateau within 1 and 2 hr for DPE and DP alpha meE, respectively. Duration of mydriatic effect was also dose-related, although more prolonged with DP alpha meE. This probably reflects differences in rate of inactivation of these compounds. The onset of IOP lowering effect of DP alpha meE was more rapid (35-45 min) when compared with DPE (1.5-2 hr) which may be due to the initial ocular hypertensive response seen with DPE. The initial rise in IOP was prevented by transection of three rectus muscles. DP alpha meE produced initial ocular hypertension only at the highest doses. The decrease of IOP lasted more than 6 hr for both drugs, returning to normal by 24 hr. No pupillary or IOP effects were seen in the contralateral eye. Denervation supersensitivity to both the pupillary and IOP responses to DP alpha meE was seen after superior cervical ganglionectomy. These findings are consistent with the hypothesis that the pupillary and IOP responses to DP alpha meE do not require intact adrenergic innervation to the eye, and that these effects are mediated by activation of postjunctional alpha-adrenoceptors. It is concluded that DP alpha meE is a potent adrenergic ocular hypotensive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

CNS alpha 2-adrenoceptor induced mydriasis in conscious rats.

Clonidine (3-300 microgram/kg, i.p.) produced dose-dependent pupillary dilation in unanesthetized rats. At low levels of illumination (30 lux), this effect was similar to that seen in anesthetized animals but was diminished under higher ambient lighting conditions. alpha Methyldopa (60 mg/kg, i.p.) produced mydriasis that took several hours to develop and was prevented by pretreatment with a dopamine beta-hydroxylase inhibitor (FLA-63). Yohimbine antagonized pupillary dilation induced by both clonidine and methyldopa. These results demonstrate that mydriasis in the conscious rat can be an effective index of CNS alpha 2-adrenoceptor activation, particularly when measured under low lighting levels.

Anesthesia↗