Biomedical subjects

M C Koss

Publications and source records attributed to M C Koss.

At least 19 recordsLinked to original sources

PubMed2003

Rilmenidine produces mydriasis in cats by stimulation of CNS alpha 2-adrenoceptors.

1. Experiments were undertaken to determine if the imidazoline/alpha2-adrenoceptor agonist, rilmenidine, would produce mydriasis in cats and, if so, to delineate its site of action and determine if this effect is mediated by imidazoline receptors or alpha2-adrenoceptors. 2. Rilmenidine produced dose-related pupillary dilator responses in pentobarbital anaesthetized cats that were independent of sympathetic innervation to the iris but were dependent upon intact parasympathetic neuronal tone. The ED50 for rilmenidine-induced pupillary dilation was approximately 200 microg kg(-1), i.v., and was sustained for at least 1 h. 3. The highly selective alpha2-adrenoceptor antagonist, RS-79948, administered either before or after rilmenidine, antagonized rilmenidine-induced mydriasis. Neuronally induced reflex inhibition of parasympathetic nerve activity was also inhibited by administration of RS-79948. 4. These results suggest that rilmenidine acts like clonidine to produce pupillary dilation by inhibition of parasympathetic tone to the iris sphincter and that this central nervous system parasympatho-inhibition is mediated by alpha2-adrenoceptors, rather than imidazoline receptors.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2001

Histamine H3 receptor-mediated inhibition of sympathetically evoked mydriasis in rats.

This study was designed to determine if the histamine H3 receptor agonist R-alpha-methylhistamine would play a role in modulation of sympathetically evoked mydriasis in anesthetized rats, and if so, to ascertain the specific receptor subtype(s) involved. Reproducible frequency-response curves of pupillary dilation were generated by stimulation of the cervical preganglionic sympathetic nerve (1-32 Hz). Systemic administration of R-alpha-methylhistamine (0.3-3.0 mg kg(-1)) produced a dose-related inhibition of the evoked mydriasis. The greatest inhibition was seen at lower frequency levels, with about 43% depression observed at 2 Hz. The specific histamine H3 receptor antagonist, clobenpropit (3.0 mg kg(-1), i.v.), blocked the inhibitory effect of R-alpha-methylhistamine, whereas neither the histamine H2 receptor antagonist, cimetidine (5.0 mg kg(-1), i.v.), nor the histamine H1 receptor antagonist, chlorpheniramine (0.5 mg kg(-1), i.v.), was effective. The histamine H2 receptor agonist, dimaprit (10 mg kg(-1), i.v.), was also without effect on the evoked mydriasis. R-alpha-methylhistamine (3.0 mg kg(-1)) did not inhibit phenylephrine-induced mydriasis. These results support the conclusion that R-alpha-methylhistamine produces inhibition of sympathetically evoked mydriasis via histamine H3 receptor stimulation, presumably by an action on presynaptic histamine H3 receptors.

Animals↗

PubMed2001

Sympathetic control of nasal blood flow in the rat mediated by alpha(1)-adrenoceptors.

Experiments were undertaken, using laser-Doppler flowmetry, to determine the nature of adrenoceptors mediating sympathetic nerve evoked nasal vasoconstrictor responses in anesthetized rats. Presence of sympathetic tone was confirmed by a large (330%) increase of nasal blood flow following section of the ipsilateral preganglionic cervical sympathetic nerve. Electrical nerve stimulation produced reproducible, frequency-related nasal vasoconstrictor responses with near maximal response, observed at less than 10 Hz. Evoked nasal vasoconstrictor responses were largely blocked with intravenous treatment with the non-selective alpha-adrenoceptor antagonists, phentolamine (5 mg kg(-1)) and phenoxybenzamine (2 mg kg(-1)), as well as with the selective alpha(1)-adrenoceptor antagonist, prazosin (300 microg kg(-1)). alpha(2)-Adrenoceptor antagonism with rauwolscine (500 microg kg(-1)) potentiated neurally evoked nasal vasoconstriction. Neither atropine (1 mg kg(-1)) nor propranolol (1 mg kg(-1)) altered the evoked responses. Rats with intact cervical sympathetic nerves responded to rauwolscine with a modest constriction. Subsequent prazosin administration produced an increase of nasal blood flow of approximately 275%. These results suggest that the nasal vasculature of the rat is under intense sympathetic tone and that the resulting neurogenic vasoconstriction is mediated exclusively by activation of alpha(1)-adrenoceptors.

Adrenergic Fibers↗

PubMed2001

Nitric oxide regulation of lingual blood flow in the rat.

The purpose of this study was to determine the role of nitric oxide in the maintenance of basal lingual blood flow in the anesthetized rat. By using laser-Doppler flowmetry, blood flow was measured from the tongue before and after treatment with the nonselective inhibitor of nitric oxide synthase, L-NAME (0.2, 2.0, and 20 mg/kg), or the selective neuronal nitric oxide synthase inhibitor, 7-nitroindazole (40 mg/kg). Other groups of rats were treated with saline, D-NAME (2.0 mg/kg), L-arginine (200 mg/kg), L-arginine + L-NAME (200 + 2.0 mg/kg), or the 7-nitroindazole vehicle. L-NAME produced a dose-related depression in blood flow in the tongue (concurrent with increased arterial blood pressure), which was attenuated by prior administration of L-arginine. Lingual blood flow depression was not seen after administration of the inactive stereoisomer, D-NAME. In addition, the neuronally specific nitric oxide synthase inhibitor, 7-nitroindazole, failed to produce a significant depression of lingual blood flow. These results suggest that the tonic release of nitric oxide from the vascular endothelium plays an important role in maintaining basal blood flow in the tongue and that neuronally released nitric oxide is not involved in maintaining basal circulation in this vascular bed.

Animals↗

PubMed2001

Effects of inhibition of nitric oxide synthase on basal anterior segment ocular blood flows and on potential autoregulatory mechanisms.

Experiments were undertaken to determine the role played by nitric oxide (NO) in basal ocular blood flow in the anterior aspect of the eye. Subsequent studies focused on existence of autoregulatory mechanisms and on the potential involvement of NO. Cats were anesthetized with pentobarbital (36 mg/kg, i.p.). A femoral artery and vein were cannulated for measuring blood pressure and for drug administration, respectively. Anterior segment blood flow was measured in a continuous fashion from the long posterior ciliary artery (LPCA) using ultrasonic flowmetry and from the anterior choroid using laser-Doppler flowmetry. A needle was placed into the anterior chamber, and autoregulatory mechanisms were studied by decreasing ocular perfusion pressure via stepwise elevations of IOP. Non-selective inhibition of NO synthase with L-NAME (20 mg/kg, i.v.) significantly decreased basal blood flow from both sites. L-NAME (5 mg/kg, i.v.) was without effect as was D-NAME (25 mg/kg, i.v.). Increasing IOP produced a linear decrease on LPCA blood flow indicating absence of autoregulation. In contrast, stepwise elevation of IOP produced a delayed, non-linear response in the anterior choroid suggestive of a strong autoregulatory response. Neither response to elevated ocular perfusion pressure was further altered by inhibition of NO synthase with L-NAME (20 mg/kg, i.v.). The results confirm previous reports that nitric oxide plays a pivotal role in maintenance of basal ocular blood flow. Autoregulation was not seen in the LPCA. In contrast, there was a clear autoregulatory response in the anterior choroid, although neither response was altered by inhibition of NO synthase.

Animals↗

PubMed2000

Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats.

Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Administration of the nonselective inhibitor of nitric oxide synthase (NOS), L-NAME (0.08-20 mg/kg i.v.), produced a dose-related increase of blood pressure associated with decreases of blood flow at all three measurement sites. Maximal blood flow depression of 50-60% was seen 30-60 min after administration of 1.25 mg/kg of L-NAME. D-NAME (1.25 mg/kg i.v.) was inactive at all sites. Subsequent administration of L-arginine partially reversed effects of L-NAME in the lingual artery and tongue, but not in the gingival circulation. The neuronally selective NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg i.p.), was devoid of effect on any of the measured parameters. These results suggest that endothelial (but not neuronally derived) NO plays an important role in control of basal blood flow in oral tissues of the cat.

Adjuvants, Anesthesia↗

PubMed2000

Effect of nitric oxide synthesis inhibition on post-occlusive choroidal blood flow in rats.

Experiments were designed to study involvement of nitric oxide on vascular responses to ocular ischemia in the anesthetized rat. Anterior choroidal blood flow was measured using laser-Doppler flowmetry. In some experiments, cerebral cortical blood flow also was measured. Ischemia was produced by either occlusion of the cephalic blood supply or more locally via a ligature tightened around the eye stalk. Arterial blood pressure and choroidal blood flow was continuously measured before, during and after a 20 min ischemic challenge. Both methods of ischemia reduced choroidal blood flow (>90%) with no consistent ocular hyperemia seen upon reperfusion. No significant differences in response pattern between the two ischemia techniques were apparent. Treatment with the non-selective inhibitor of nitric oxide (L-NAME 2 mg/kg, i.v.) did not alter either basal choroidal blood flow or the pattern of reperfusion. A larger dose of L-NAME (50 mg/kg, i.v.) reduced both basal choroidal blood flow and the final reperfusion level (most likely due to continued depression of the basal ocular choroidal blood flow). Neither D-NAME nor the neuronal nitric oxide synthase inhibitor, 7-nitroindazole, altered basal anterior choroidal blood flow or the reperfusion pattern seen after reperfusion. The results confirm our previous observations that inhibition of endothelial nitric oxide lowers. basal choroidal blood flow in the rat eye. However, in contrast to the cerebral circulation where L-NAME greatly attenuates initial reperfusion to the cerebral cortex, inhibition of nitric oxide synthase does not appear to notably further influence anterior choroidal reperfusion.

Animals↗

PubMed1999

Sympathetic vasodilation in the rat anterior choroid mediated by beta(1)-adrenoceptors.

Electrical stimulation of the preganglionic superior cervical nerve produced a frequency-dependent vasoconstrictor response in the anterior choroidal blood vessels of the eye of anesthetized rats. Systemic administration of phentolamine (5 mg kg(-1)) reversed the vasoconstriction to a vasodilator response. This sympathetic-evoked vasodilation was not antagonized by inhibition of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) (20 mg kg(-1)) or by inhibition of cyclo-oxygenase with indomethacin (20 mg kg(-1)). Intravenous administration of propranolol (1 mg kg(-1)), as well as selective beta(1)-adrenoceptor antagonists atenolol (3 mg kg(-1)), timolol (0.3 mg kg(-1)), and betaxolol (0.1 mg kg(-1)), totally abolished the sympathetic nerve evoked ocular vasodilation. In contrast, the selective beta(2)-adrenoceptor antagonist, ICI-118, 551 ((+/-)-1-[2, 3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2- butanol) (0.3 mg kg(-1), i.v.), was without effect. These results support the conclusion that the residual sympathetic ocular vasodilation observed in the rat anterior choroid after alpha-adrenoceptor blockade is mediated exclusively by neurogenic release of norepinephrine acting on vascular beta(1)-adrenoceptors.

Adrenergic alpha-Antagonists↗

PubMed1999

Functional role of nitric oxide in regulation of ocular blood flow.

Nitric oxide generated by three distinct enzyme systems appears to play a critical role in many diverse physiological processes. Using both conventional and immunohistochemical techniques, nitric oxide synthases have been identified throughout the body, including all regions of the eye. A large number of in vitro and in vivo preparations have been utilized showing nitric oxide to have an important role in regulation of regional ocular blood flow. Nitric oxide-mediated control of basal ocular blood flow is demonstrated by vasoconstriction seen in experiments where vascular endothelial cells are removed, or when nitric oxide synthase is inhibited. The endogenous source of nitric oxide in the eye appears to be both endothelial and neural. In addition, administration of drugs that can 'donate' nitric oxide produces vasodilation of the eye vasculature. Local vasodilation in response to illumination of the retina is controlled by generation and release of nitric oxide, whereas most other physiological adjustments of ocular blood flow (i.e., autoregulation and responses to altered blood gas levels) seem to be relatively independent of nitric oxide mechanisms. Nitric oxide is implicated in a variety of ocular pathophysiological states including uveitis, retinal ischemic disease, diabetes and glaucoma.

Animals↗

PubMed1999

Analysis of blood flow in the long posterior ciliary artery of the cat.

PURPOSE: Experiments were undertaken to use a new technique for direct on-line measurement of blood flow in the long posterior ciliary artery (LPCA) in cats and to evaluate possible physiological mechanisms controlling blood flow in the vascular beds perfused by this artery. METHODS: Blood flow in the temporal LPCA was measured on a continuous basis using ultrasonic flowmetry in anesthetized cats. Effects of acute sectioning of the sympathetic nerve and changes in LPCA and cerebral blood flows in response to altered levels of inspired CO2 and O2 were tested in some animals. In others, the presence of vascular autoregulatory mechanisms in response to stepwise elevations of intraocular pressure was studied. RESULTS: Blood flow in the temporal LPCA averaged 0.58+/-0.03 ml/min in 45 cats anesthetized with pentobarbital. Basal LPCA blood flow was not altered by acute sectioning of the sympathetic nerve or by changes in low levels of inspired CO2 and O2, although 10% CO2 caused a modest increase. Stepwise elevations of intraocular pressure resulted in comparable stepwise decreases of LPCA blood flow, with perfusion pressure declining in a linear manner throughout the perfusion-pressure range. CONCLUSIONS: Ultrasonic flowmetry seems to be a useful tool for continuous on-line measurement of LPCA blood flow in the cat eye. Blood flow to vascular beds perfused by this artery does not seem to be under sympathetic neural control and is refractory to modest alterations of blood gas levels of CO2 and O2. Blood vessels perfused by the LPCA show no clear autoregulatory mechanisms.

Animals↗

PubMed1998

Sympathetic vasoconstriction in the rat anterior choroid is mediated by alpha1-adrenoceptors.

These experiments were undertaken in an attempt to use laser-Doppler flowmetry to measure anterior choroidal blood flow in the anesthetized rat and to study the mechanism by which sympathetic nerve stimulation might produce vasoconstriction in this vascular bed. Electrical stimulation of the preganglionic cervical sympathetic nerve produced reproducible, frequency-related ocular vasoconstrictor responses with maximal vasoconstriction seen at about 32 Hz. Ocular vasoconstrictor responses were blocked by intravenous treatment with the nonselective alpha-adrenoceptor antagonists, phentolamine (5 mg kg(-1)) and phenoxybenzamine (2 mg kg(-1)), as well as with the selective alpha1-adrenoceptor antagonist, prazosin (0.3 mg kg(-1)). In contrast, the selective alpha2-adrenoceptor blocker, rauwolscine (0.5 mg kg(-1)), only potentiated the vasoconstriction. Neither intravenous atropine (1 mg kg(-1)) nor propranolol (1 mg kg(-1)) altered the magnitude of neurally evoked vasoconstriction. These results demonstrate the usefulness of laser-Doppler flowmetry in studies of the rat anterior choroidal circulation and suggest that adrenergic neurogenic vasoconstriction in the anterior segment of the rat eye is mediated almost exclusively by alpha1-adrenoceptor mechanisms.

Adrenergic Antagonists↗

PubMed1998

Role of nitric oxide in post-ischemic cerebral hyperemia in anesthetized rats.

This study was undertaken to determine the extent to which nitric oxide (NO) mechanisms are involved in cerebral hyperemia following global brain ischemia. The vertebral arteries were cauterized through the first alar foramina in anesthetized male Sprague-Dawley rats and followed by 20-min occlusion of the common carotid arteries. Blood flow from the parietal cerebral cortex was measured using laser-Doppler flowmetry. In saline-treated animals, carotid occlusion reduced cerebral blood flow by approximately 95% with a maximal hyperemia of about 400% observed after 15 min of reperfusion. Pre-treatment with the nonspecific NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester; 2, 10 and 50 mg kg(-1)), produced dose-related depression of post-ischemic hyperemia, whereas D-NAME (10 mg kg(-1)) was inactive. Pre-treatment with L-arginine (300 mg kg(-1), i.v.) prevented L-NAME attenuation of cerebral hyperemia. The selective neuronal NO synthase inhibitor, 7-nitroindazole (30 mg kg(-1)), was without significant depressant effect. These results suggest that NO (largely from vascular endothelium) is instrumental in development of post-ischemic cerebral hyperemia.

Anesthesia↗

PubMed1998

Role of nitric oxide in maintenance of basal anterior choroidal blood flow in rats.

PURPOSE: The aim of this study was to use laser Doppler flowmetry to measure anterior choroidal blood flow in the anesthetized rat and to determine the role of nitric oxide (NO) in the maintenance of basal ocular blood flow in vivo. METHODS: By using laser Doppler flowmetry, blood flow from the anterior choroid in pentobarbital-anesthetized rats was measured continuously. Graded single doses (0.03-300 mg/kg) of the nonselective NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) were administered intravenously to establish dose-response relationships. Other groups of animals were tested with L-NAME after the prior administration of L-arginine, with D-NAME, or with the selective neural NO synthase inhibitor 7-nitroindazole. RESULTS: Intravenous administration of L-NAME produced a dose-related depression of anterior choroidal blood flow in the 0.3- to 30-mg/kg range. Maximal depression of approximately 60% occurred at the 30-mg/kg dose, peaked at approximately 30 minutes, and lasted throughout the 60-minute experimental period. At 10 mg/kg, L-NAME reduced ocular blood flow by approximately 50%, an effect that was abolished by pretreatment with intravenous L-arginine (300 mg/kg). Both D-NAME (10 mg/kg, intravenously) and 7-nitroindazole (50 mg/kg, intraperitoneally) were inactive with regard to ocular blood flow depression. CONCLUSIONS: Laser Doppler flowmetry appears to be a useful tool for continuous, online measurement of anterior choroidal blood flow in the rat eye. Results with L-NAME and 7-nitroindazole suggest that local tonic generation of endothelial NO plays an important role in the maintenance of basal anterior choroidal blood flow in this species.

Animals↗

PubMed1997

Effect of N(G)-nitro-L-arginine methyl ester on functionally characterized muscarinic receptors in anesthetized cats.

This study was undertaken to determine if the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), is a competitive antagonist of muscarinic receptors in vivo. Cats were anesthetized with pentobarbital (36 mg/kg, i.p.). Five peripheral muscarinic responses were characterized based on their sensitivity to intravenous administration of atropine (1-100 microg/kg), pirenzepine (1-100 microg/kg) or gallamine (30-3000 microg/kg) as follows: (1) muscarinic ganglionic transmission through the superior cervical ganglion to the nictitating membrane (M1), (2) electrically elicited vagal bradycardia (M2), (3) neurally evoked sudomotor responses (M3; non-endothelial), (4) basal pupil tone in sympathectomized cats (M3; non-endothelial) and (5) methacholine-induced depression of arterial blood pressure (M3; endothelial). Additional groups of animals were administered L-NAME (50 mg/kg, i.v.) to determine if this agent would alter activation of these muscarinic systems. L-NAME was devoid of effect on responses elicited by stimulation of muscarinic M1, M2 and M3 (non-endothelial) receptors. In contrast, L-NAME significantly reduced the depressor responses to i.v. methacholine (M3; endothelial), as did its non-alkyl ester congener, L-NA (NG-nitro-L-arginine; 25 mg/kg, i.v.). These results support the conclusion that although L-NAME inhibits synthesis of nitric oxide in vascular endothelial cells, it is not a generalized muscarinic receptor antagonist in vivo.

Animals↗

PubMed1997

Functional characterization of peripheral muscarinic subtypes in anesthetized cats.

This investigation was undertaken to characterize the muscarinic receptor subtypes involved in methacholine-induced vasodilation, vagal bradycardia, neurally-evoked sudomotor responses and sympathetic muscarinic ganglionic transmission in anesthetized cats. Dose-response curves were constructed using the putatively selective antagonists pirenzepine (M1), gallamine (M2) and 4-DAMP (M3: 4-diphenyl-acetoxy-N-methylpiperidine) and compared with the non-selective blocker, atropine. Methacholine hypotension and evoked sudomotor responses exhibited an M3 muscarinic receptor profile with the following potency relationships: atropine > or = 4-DAMP > pirenzepine >> gallamine. Vagal bradycardia (M2) was antagonized by gallamine and exhibited a lower relative sensitivity to 4-DAMP when corrected for atropine effect. Pirenzepine was inactive in inhibition of bradycardia but was highly potent against transmission in the sympathetic ganglion (M1) with the following potency relationships: atropine > or = pirenzepine > 4-DAMP >> gallamine. In comparison with atropine, 4-DAMP exhibited a significantly lower potency for M1 and M2 muscarinic receptors as compared to its effect on the M3 muscarinic receptor subtypes.

Animals↗

PubMed1997

Assessment of muscarinic transmission in the superior cervical and ciliary ganglion of the cat.

This study was undertaken to determine if muscarinic mechanisms are involved in synaptic transmission in the parasympathetic ciliary ganglion as has been clearly shown for sympathetic ganglia. Cats were anesthetized, and following topical ephedrine, pupillary constrictions were elicited by electrical stimulation of the intracranial oculomotor nucleus. Nictitating membrane contractions were evoked by electrical stimulation of the preganglionic cervical nerve. Frequency-response curves were repeated after infusion with hexamethonium (0.6-1.0 mg/kg min-1) and after subsequent administration of atropine (500 micrograms/kg. i.v.). In other experiments, effects of nicotinic (DMPP) and muscarinic (McN-A-343) agonists on postganglionic ciliary nerve activity were measured. Treatment with hexamethonium reduced nictitating membrane responses at all frequencies of stimulation (by about 75% at 16-32 Hz). The residual nictitating membrane contractions were subsequently blocked by the addition of atropine. In contrast, hexamethonium totally abolished miosis produced by CNS preganglionic oculomotor nerve stimulation. The nicotinic agonist, DMPP, produced nictitating membrane contractions, miosis, and increased ciliary nerve firing. In contrast, McN-A-343 contracted the nictitating membrane but failed to increase postganglionic ciliary nerve activity. These results suggest that, unlike sympathetic ganglia, a significant degree of muscarinic transmission does not occur in the parasympathetic ciliary ganglion.

Animals↗

PubMed1997

Role of nitric oxide in cutaneous blood flow increases in the rat hindpaw during dorsal column stimulation.

OBJECTIVE: Dorsal column stimulation (DCS) increases blood flow to the extremities and may produce a limb-saving effect in addition to treatment of refractory chronic pain in patients with peripheral vascular disease. The purpose of this study was to examine the importance of nitric oxide in cutaneous vasodilation caused by DCS. METHODS: Male Sprague-Dawley rats were anesthetized with pentobarbital (60 mg/kg, intraperitoneally). A unipolar ball electrode was placed on the left-side of the exposed spinal cord at approximately L1-L2. Blood flow was concurrently recorded from both hindpaw foot pads with laser doppler flowmeters. Blood flow responses were assessed during 1 minute of DCS (0.6 mA at 50 Hz, 0.2-ms pulse) at 10-minute intervals. Nitric oxide synthase was inhibited with NG-nitro-L-arginine methyl ester (L-NAME). Four groups of animals were examined. The first and second groups involved examination of the effects of DCS after 2 and 10 mg/kg L-NAME, respectively. In the third group, the effect of another nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (10 mg/kg), was examined on the responses to DCS. The fourth group of animals entailed comparison of the effects of DCS under control conditions, after the nicotinic receptor antagonist, hexamethonium (10 mg/kg), and during the combined presence of hexamethonium and L-NAME (10 mg/kg). RESULTS: L-NAME markedly attenuated the cutaneous blood flow increases caused by DCS at doses of 2 or 10 mg/kg. Similarly, NG-monomethyl-L-arginine also attenuated the DCS response. Hexamethonium did not affect the cutaneous vasodilation caused by DCS. After hexamethonium, L-NAME no longer attenuated the DCS response. CONCLUSION: Our results demonstrated that nitric oxide played a significant role in producing the DCS-induced increase in rat cutaneous hindpaw blood flow. The involvement of nitric oxide does not require the presence of autonomic efferent function; however, ganglionic blockade may unmask a mechanism for vasodilation during DCS that is independent of nitric oxide release.

Animals↗

PubMed1995

Analysis of miosis produced by McN-A-343 in anesthetized cats.

McN-A-343 is a selective M1 muscarinic agonist that stimulates muscarinic transmission in sympathetic ganglia. In preliminary experiments, we observed that i.v. McN-A-343 produced miosis in cats in the presence of nicotinic ganglionic blockade. This project was undertaken to ascertain the mechanism and site(s) by which McN-A-343 produces pupil constriction in the cat. Cats were anesthetized, the vago-sympathetic nerve trunks sectioned, and one superior cervical ganglion (SCG) was removed. Bilateral pupillary and nictitating membrane (NM) dose-response curves in response to i.v. McN-A-343 (6.25-1600 micrograms/kg) were generated during infusion of hexamethonium to block nicotinic ganglionic transmission. Experiments were repeated in animals pretreated with atropine or with the M1 muscarinic receptor antagonist, pirenzepine. In one series of experiments, selective lesions of the ciliary ganglia were undertaken. McN-A-343 produced an atropine sensitive dose-related miosis that was potentiated by removal of the SCG but not antagonized by either pirenzepine or by removal of the ciliary ganglion. In contrast, contraction of the NM was blocked by both atropine and pirenzepine and was dependent on intact sympathetic ganglionic innervation. McN-A-343 induced pupillary constriction appears to be due to direct stimulation of the iris sphincter by stimulation of M3 rather than M1 muscarinic receptors. In contrast to sympathetic ganglia where muscarinic transmission (via M1 muscarinic receptors) can readily be demonstrated, these results suggest a lack of muscarinic transmission in the parasympathetic ciliary ganglion.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗