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PubMed1985

Effect of paraventricular nucleus lesions on cardiovascular responses elicited by stimulation of the subfornical organ in the rat.

It has recently been reported that stimulation of the region of the subfornical organ (SFO) elicits an increase in arterial pressure. However, the mechanisms and forebrain neural circuitry that are involved in this cardiovascular response have not been elucidated. The present study was done in urethane-anaesthetized rats to determine whether selective activation of SFO neurons elicit cardiovascular responses and whether these responses were mediated by a pathway involving the paraventricular nucleus of the hypothalamus (PVH). Stimulation sites which required the lowest threshold current (30 microA) to elicit a pressor response and at which the largest rise in mean arterial pressure (MAP; 22 +/- 2 mmHg) was elicited at a constant current intensity (150 microA) were histologically localized in the region of the SFO. Short (mean peak latency; 4 +/- 2 s) and long (mean peak latency; 61 +/- 8 s) latency increases in MAP were observed during and after electrical stimulation of the SFO, respectively. Cardiac slowing accompanied the short latency pressor response and cardioacceleration was observed in most (57%) of the cases to accompany the late pressor response. Microinjection of L-glutamate into the SFO consistently elicited cardiovascular responses qualitatively similar to those observed during electrical stimulation. Ganglionic blockade abolished the short latency increase in MAP and the accompanying bradycardia. However, the long latency pressor and cardioacceleratory responses were not altered by ganglionic blockade and adrenalectomy. Selective bilateral electrolytic or kainic acid lesions of the region of the PVH significantly attenuated the cardiovascular responses elicited by stimulation of the SFO. These data suggest that activation of neurons in the SFO elicit cardiovascular responses partially mediated by sympathetic outflow through a neural pathway involving the PVH.

Adrenalectomy↗

PubMed2000

Evidence for nitroxidergic innervation in monkey ophthalmic arteries in vivo and in vitro.

In anesthetized monkeys, electrical stimulation (ES) of the pterygopalatine or geniculate ganglion dilated the ipsilateral ophthalmic artery (OA). The induced vasodilatation was unaffected by phentolamine but potentiated by atropine. Intravenous N(G)-nitro-L-arginine (L-NNA) abolished the response, which was restored by L-arginine. Hexamethonium-abolished vasodilator responses induced solely by geniculate ganglionic stimulation. The L-NNA constricted OA; L-arginine reversed the effect. Destruction of the pterygopalatine ganglion constricted the ipsilateral artery. Helical strips of OA isolated under deep anesthesia from monkeys, denuded of endothelium, responded to transmural ES with relaxations, which were abolished by tetrodotoxin and L-NNA but were potentiated by atropine. It is concluded that neurogenic vasodilatation of monkey OA is mediated by nerve-derived nitric oxide (NO), and the nerve is originated from the ipsilateral pterygopalatine ganglion that is innervated by cholinergic neurons from the brain stem via the geniculate ganglion. The OA appears to be dilated by mediation of NO continuously liberated from nerves that receive tonic discharges from the vasomotor center. Acetylcholine liberated from postganglionic cholinergic nerves would impair the release of neurogenic NO.

Animals↗

PubMed1991

Presynaptic facilitation by the new nootropic drug nebracetam, of ganglionic muscarinic transmission in the dog cardiac sympathetic ganglion.

Effects of nebracetam (4-aminomethyl-1-benzylpyrrolidine-2-one hemifumarate, WEB 1881 FU, CAS 118607-07-1), a new nootropic drug, on impulse transmission in the cardiac sympathetic ganglia were studied in spinal dogs by monitoring heart rate as an indicator of the ganglionic function. The ganglionic stimulants were given directly into the cardiac sympathetic ganglia through the right subclavian artery (i.a.). Nebracetam, 5 mg/kg, i.v. caused a slight and temporal increase in heart rate. After nebracetam, the frequency-response curves of heart rate for preganglionic stellate stimulation (0.25-4 Hz) were not altered in the untreated and atropine-pretreated animals, but the curves (2.5-40 Hz) were shifted to the left in the hexamethonium-pretreated animals. The enhancement of ganglionic muscarinic transmission was dose-dependent on nebracetam i.v. at doses ranging from 0.5 to 15 mg/kg, with a maximal effect at 5 mg/kg. This enhanced muscarinic transmission by nebracetam was almost abolished after subsequent administration of pirenzepine 0.5 mg/kg i.v. The enhancement in the muscarinic transmission by nebracetam was also eliminated after depletion of acetylcholine at preganglionic sites caused by treatment with hemicholinium-3 in combination with preganglionic stimulation. Furthermore, nebracetam failed to affect dose-dependent post-ganglionic stimulation by McN-A-343 (1-32 micrograms), 1,1-dimethyl-4-phenylpiperazinium (1-32 micrograms) and angiotensin II (0.1 and 0.2 micrograms) administered i.a. directly to the ganglia. These results suggest that nebracetam facilitates the ganglionic muscarinic transmission through acting on presynaptic sites.

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

PubMed1992

Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation.

We investigated the effects of unilateral electrical trigeminal ganglion stimulation (0.1 or 1.0 mA, 5 Hz, 5 ms, 5 min) on the morphology of blood vessels within the rat dura mater and tongue using light and transmission electron microscopy. Stimulation at both intensities caused changes which were confined to the ipsilateral post-capillary venules except in the tongue where arterioles were affected as well. Changes were more marked after 1.0 mA. Dramatic increases in the numbers of endothelial pinocytotic vesicles were found along the luminal and abluminal surfaces ipsilateral to the stimulation. Tight junctions remained largely intact, except that injected ferritin particles were occasionally trapped inside these junctions. Cytoplasmic microvilli and endothelial blebs were sometimes present as well. Approximately 80% of the examined dural post-capillary venules showed one or more of these endothelial changes. Horseradish peroxidase injected intravenously 5 min prior to stimulation was detected in the extracellular space surrounding dural blood vessels and within pinocytotic vesicles. Ferritin injected similarly, was also localized in post-capillary venule walls, interstitial spaces, intraendothelial vesicles and in vacuoles. Platelet accumulation and aggregation were present in approximately 10% of post-capillary venules in dura and tongue. These changes were associated with mast cell secretion, but neither vascular nor mast cell activation was observed in adult rats in whom C-fibers were destroyed during the neonatal period with capsaicin. The present observations provide morphological evidence which supports findings from previously reported albumin tracer studies suggesting enhanced transport and endothelial activation following electrical stimulation of small caliber afferent fibers.

Animals↗

PubMed1976

Mossy fiber neck and second-order labyrinthine projections to cat flocculus.

In five decerebrate cats and in two under N2O-O2 anesthesia, a bipolar electrode array was inserted into a granular layer in the rostral flocculus. At this location MF field potentials were evoked by stimulation of the ipsilateral vestibular nerve and of the C2 dorsal root ganglion. Stimulation through the array was used to fire brain stem neurons antidromically. The activity of these neurons was recorded extracellularly with glass microelectrodes. Stimulation of the C2 dorsal root ganglion evoked in the caudal lateral brain stem a field potential caused by the arrival of impulses in primary afferent fibers. Cells projecting to the flocculus also responded to the stimulus, usually monosynaptically. These neurons were fired by stimulation of the area of the atlantoaxial joint. They did not respond to stimulation of the contralateral C2 dorsal root ganglion, and responded only rarely to stimulation of the dorsal rami of the C2 and C3 spinal nerves. Stimulation of the vestibular nerve was ineffective. Another group of cells projecting to the flocculus was fired at short latency by stimulation of the ipsilateral vestibular nerve. These neurons were usually inhibited by stimulation of the contralateral vestibular nerve. They were not affected by stimulation of any neck afferents. The location of many recording locations was identified by means of fast green dye marks. Most neurons relaying neck activity were in group x of Brodal and Pompeiano (4), a few were in the external cuneate nucleus, and one was in the descending vestibular nucleus. Neurons relaying labyrinthine activity were in the descending vestibular nucleus; one was found in the medial nucleus, in which tracks were made only rarely. There are two parallel pathways relaying neck and labyrinthine activity to the flocculus. While they are separate at the level of the brain stem, they converge in the same rostral areas of the flocculus. The neck afferent information may be required for proper performance of the flocculus in eye-movement control.

Animals↗

PubMed1978

Slowly-developing depolarization of neurones in the guinea-pig inferior mesenteric ganglion following repetitive stimulation of the preganglionic nerves.

Intracellular recordings were made from cells of the isolated guinea-pig inferior mesenteric ganglion. Stimulation of both hypogastric nerves at 30 Hz for 2 sec caused a slowly developing depolarization (SD) and fall in cell input resistance which reached a peak 10-30 sec after the end of stimulation. The amplitude of the SD was increased in a graded manner if the stimulus voltage was increased. The SD was unaffected by tubocurarine, atropine or guanethidine, but was blocked by removing external Ca. These results suggested that the SD was caused by the release of some substance from a large number of nerve terminals.

Animals↗

PubMed1975

The effect of vagus nerve stimulation upon vulnerability of the canine ventricle: role of sympathetic-parasympathetic interactions.

The effect of vagus nerve stimulation (VNS) upon ventricular vulnerability was studied in 30 mongrel dogs subjected to varying levels of adrenergic stimulation. Vulnerability was assessed both by determining the minimum current required to produce ventricular fibrillation (VF threshold) and by plotting VF threshold throughout the vulnerable period (VF zone). Chloralose-anesthetized animals were studied by means of sequential pulses applied to the apex of the right ventricular endocardium. Testing was carried out in closed-chest dogs, in open-chest dogs with and without left stellate ganglion stimulation (LSGS), and in open- and closed-chest dogs pretreated with propranolol. In the absence of adrenergic stimulation. VNS was without significant effect on either the VF threshold or the VF zone under closed- or open-chest conditions. During LSGS, however, VNS was associated with a 93 +/- 22% (mean +/- SE) increase in VF threshold (P less than 0.01) and constriction of the VF zone. Vagus nerve stimulation combined with LSGS raised VF threshold to the control value, but not beyond. After beta-adrenergic blockade with propranolol, VNS was without effect on VF threshold in either open- or closed-chest animals. It is concluded that augmented sympathetic tone is a precondition for a VNS-induced elevation in VF threshold. The vagal effect is indirect and is expressed by opposing the effects of heightened adrenergic tone on ventricular vulnerability.

Acetylcholine↗

PubMed1986

Nicotinic and muscarinic agonists, phorbol esters, and agents which raise cyclic AMP levels phosphorylate distinct groups of proteins in the superior cervical ganglion.

The phosphorylation of proteins in the superior cervical ganglion of the rat was investigated. Ganglia were incubated with 32Pi, and the 32P-labeled proteins in the ganglion were separated by two-dimensional electrophoresis and visualized by autoradiography. Approximately 40 distinct phosphoproteins could be visualized by these methods. The most heavily labeled ganglionic protein was an acidic protein with an Mr of approximately 83,000. Tyrosine hydroxylase was identified as a doublet of two closely-migrating radioactive spots. Treatment of intact ganglia with depolarizing agents, nicotinic and muscarinic agonists, phorbol esters, and agents that increase the content of cyclic adenosine 3':5'-monophosphate in the ganglion stimulated the incorporation of 32Pi into distinct but overlapping groups of phosphoproteins. All of these agents increased the phosphorylation of tyrosine hydroxylase. In contrast, only phorbol esters and muscarinic agonists increased the phosphorylation of the 83,000 ganglionic phosphoprotein. Our data are consistent with the idea that the various classes of agonists may activate distinct protein kinases in the ganglion.

Animals↗

PubMed1996

Prostaglandin E2 modulates neurally induced nonadrenergic, noncholinergic gastric relaxations in the rabbit in vivo.

BACKGROUND & AIMS: Prostaglandin (PG) E2 has been shown to modulate adrenergic and cholinergic neurotransmission in the gut. This study investigated PGE2 influence on vagally induced, nonadrenergic, noncholinergic (NANC) gastric relaxations. METHODS: Mechanical activity of the stomach was recorded in anesthetized rabbits. RESULTS: In atropine-treated animals, electrical vagal stimulation or arterial bolus injection of the ganglion stimulant dimethyl phenylpiperazinium iodide (DMPP) evoked inhibitory responses that varied from a brisk relaxation, interrupted by a poststimulus excitatory motility (biphasic response), to a long-lasting relaxation (monophasic response). PGE2 reduced and, at the highest doses, abolished the neurally induced relaxant responses elicited either by vagal stimulation or DMPP administration but did not affect the gastric relaxation caused by adenosine triphosphate (ATP), sodium nitroprusside (SNP), or vasoactive intestinal polypeptide (VIP). ATP or 2-methylthioadenosine triphosphate (2-MeSATP) reduced and then suppressed vagally induced inhibitory motility; the relaxant responses elicited by SNP, VIP, and ATP itself were not influenced. After administration of the prostaglandin synthesis inhibitor suprofen, ATP and 2-MeSATP failed to block vagally induced inhibitory responses. Arterial infusion of adenosine at the highest rates did not influence the amplitude of the vagally induced relaxant responses. Following theophylline administration, ATP still blocked the relaxation elicited by vagal stimulation. CONCLUSIONS: PGE2 may modulate NANC inhibitory neurotransmission in the stomach. The effects of ATP on the neurally induced NANC gastric relaxation may be caused by PGE2.

Adenosine↗

PubMed1985

Evidence for substance P-immunoreactive spinal afferents that mediate bronchoconstriction.

The origin and functional role of capsaicin-sensitive substance P-(SP-) immunoreactive (IR) nerve fibres in the lower airways were studied in the guinea-pig. Stellatectomy caused a significant reduction of SP-IR in the lung and pulmonary artery. Immunohistochemical analysis, however, did not reveal any clear-cut change in the number and distribution of SP-IR fibres in the lung of these animals. After combined stellatectomy plus local capsaicin treatment of the vagal nerves, most SP-IR nerves disappeared in the lower airways. The bronchoconstriction induced by capsaicin was significantly reduced after stellatectomy and abolished after stellatectomy plus capsaicin pretreatment of the vagal nerves. Ether inhalation caused bronchoconstriction, which was not influenced by stellatectomy but markedly reduced by combined capsaicin treatment of vagal nerves and stellatectomy. Stellate ganglion stimulation in animals that had been chemically sympathectomized by 6-OH-dopamine caused bronchoconstriction, which was resistant to cholinergic or adrenergic receptor blockade. This response was absent after systemic capsaicin pretreatment, suggesting that it was due to antidromic stimulation of afferent fibres traversing the stellate ganglion. In conclusion, the present data suggest that the lower airways receive SP-IR capsaicin-sensitive C-fibre afferents of both vagal and spinal origin. These sensory fibres seem to have branches both within the bronchial smooth muscle and around blood vessels.

Afferent Pathways↗

PubMed1991

The role of alpha adrenoceptor subtypes in sympathetic control of the acral-cutaneous microcirculation.

In pithed and anesthetized rats, laser-Doppler flowmetry was used to evaluate the role of alpha-1 and alpha-2 adrenoceptors in mediating sympathetic responses in acral regions of the cutaneous circulation. The intravenous administration of the selective alpha-1 agonist, phenylephrine, was a more potent vasopressor agent than BH-T 933 (a selective alpha-2 adrenoceptor agonist) in pithed rats. However, BH-T 933 was more potent and more efficacious than phenylephrine in reducing cutaneous microvascular perfusion (CP). BH-T 933 also caused a greater increase in cutaneous microvascular resistance. Neural and humoral sympathetic effects on CP were characterized with selective alpha-1 and alpha-2 adrenoceptor antagonists (prazosin and rauwolscine, respectively). It was found that frequency-related reductions in CP elicited by sciatic nerve stimulation were antagonized by prazosin, but not by rauwolscine. In fact, rauwolscine enhanced neurally evoked reductions in CP at the highest stimulation frequencies. However, both prazosin and rauwolscine antagonized reductions in CP elicited by electrical stimulation of the thoracolumbar outflow (sympathoadrenal activation). Ganglionic stimulation (intravenous 1,1-dimethyl-4-phenylpiperazinium) also caused a profound, transient reduction in CP that was abolished by rauwolscine, but was not significantly altered by prazosin. In contrast, 1,1-dimethyl-4-phenylpiperazinium-induced increases in mean arterial pressure were reduced by prazosin, but not by rauwolscine. In ketamine-anesthetized rats, rauwolscine caused a dose-related increase in CP without altering mean arterial pressure, whereas prazosin lowered mean arterial pressure but did not alter CP. We conclude that acral regions of the cutaneous vasculature are more sensitive to alpha-2 vis-a-vis alpha-1 adrenoceptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Tachyphylaxis and sensitization to nicotine-induced tachycardiac and pressor effects after nicotine infusions.

This work examined the effects of nicotine on mean arterial pressure and heart rate in non-anesthetized spinal rats. Nicotine (200 mg/kg) was administered as a single bolus, as infusions lasting 7.5, 15 or 30 min, and as a post-infusion bolus. A nicotine bolus increased pressure and rate. These effects were less marked as the rate of infusion decreased. The infusions affected differentially the effects of a subsequent bolus. Thus, while tachycardia was decreased, the blood pressure rise was increased. An initial transient bradycardia was observed after bolus administration, but not during infusions; this effect was unchanged after post-infusion boluses. Pharmacological analysis indicated that tachycardia and bradycardia were predominantly due to ganglionic stimulation, while adrenal and sympathetic nerve catecholamine release played a major role in the pressor response. These results indicate that slow nicotine infusions do not induce tachyphylaxis for all of the cardiovascular effects of a subsequent bolus, and that development of acute tolerance appears to depend on the mechanism of action of the response.

Animals↗

PubMed2006

Disconnection between activation and desensitization of autonomic nicotinic receptors by nicotine and cotinine.

Cotinine is the major metabolite of nicotine in humans, and the substance greatly outlasts the presence of nicotine in the body. Recently, cotinine has been shown to exert pharmacological properties of its own that include potential cognition enhancement, anti-psychotic activity, and cytoprotection. Since the metabolite is generally less potent than nicotine in vivo, we considered whether part of cotinine's efficacy could be related to a reduced ability to desensitize nicotinic receptors as compared with nicotine. Rats freely moving in their home cages were instrumented to allow ongoing measurement of mean arterial blood pressure (MAP). The ganglionic stimulant dimethylphenylpiperazinium (DMPP) maximally increased MAP by 25mmHg. Slow (20min) i.v. infusion of nicotine (0.25-1micromol) produced no change in resting MAP, but the pressor response to subsequent injection of DMPP was significantly attenuated in a dose-dependent manner by up to 51%. Pre-infusion of equivalent doses of cotinine produced the same maximal degree of inhibition of the response to DMPP. Discrete i.v. injections of nicotine also produced a dose dependent increase in MAP of up to 43mmHg after the highest tolerated dose. In contrast, injection of cotinine produced no significant change in MAP up to 13 times the highest dose of nicotine. These results illustrate the disconnection between nicotinic receptor activation and receptor desensitization, and they suggest that cotinine's pharmacological actions are either mediated through partial desensitization, or through non-ganglionic subtypes of nicotinic receptors.

Animals↗

PubMed2000

Dynamic exercise attenuates sympathetic responsiveness of canine vascular smooth muscle.

The phenomenon of reduced responsiveness of the skeletal muscle arterial vasculature to sympathetic activation during exercise (sympatholysis) remains controversial. The purpose of this study was to examine the vascular effects of sympathoactivation in dynamically exercising skeletal muscle. Mongrel dogs (19-24 kg) were instrumented chronically with transit-time ultrasonic flow probes on the external iliac arteries. After pretreatment with atropine (0.2 mg/kg), an intravenous bolus (4 microg/kg) of a nicotinic ganglion stimulant [1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)] was given at rest and during treadmill exercise at graded intensities. Administration of DMPP was associated with prompt reductions in iliac blood flow and increases in arterial pressure under all conditions. There were significant reductions (P < 0.05) in iliac vascular conductance of 58 +/- 4 (SE), 48 +/- 3, 36 +/- 5, and 16 +/- 3% at rest, 3 miles/h and 0% grade, 6 miles/h and 0% grade, and 6 miles/h and 15% grade, respectively. These data demonstrate that activation of postganglionic sympathetic nerves with DMPP caused vasoconstriction in the skeletal muscle vasculature at rest and during exercise. Additionally, the magnitude of vasoconstriction was inversely related to exercise intensity. These results support the concept of exercise sympatholysis.

Animals↗

PubMed1993

Mechanism of intragastric tetramethylammonium protection against 40% ethanol injury in rat stomach.

The effect of tetramethylammonium (TMA), a ganglionic stimulant, on gastric mucosal injury induced by 40% ethanol was examined. In studies I-III, rats were treated with intragastric vehicle or TMA (1 or 10 mg/kg). In study I, 1 hr after the treatment, 40% ethanol was given intragastrically. The length of the linear corpus mucosal lesions was measured unbiasedly with a caliper after another hour. In study II, mean blood pressure was assessed before and after the treatment. In study III, 1 hr after the treatment, gastric mucus and juice volumes, and titratable acid were measured. In study IV, 40% ethanol (10 ml/kg) was administered intragastrically immediately after 0.2 or 1.4 ml of intragastric vehicle treatment. One hour later, gastric lesions score was assessed as in study I. Results show that (1) intragastric TMA dose-dependently protected against 40% ethanol-induced gastric injury; (2) neither dose of intragastric TMA increased mean blood pressure; (3) there was a dose-related increase in gastric mucus secretion for TMA 1 and 10 mg/kg, and a significant increase in gastric juice volume only for TMA 10 mg/kg; and (4) the rats treated with 1.4 ml of vehicle plus 40% ethanol had significantly less injury than those treated with 0.2 ml of vehicle plus 40% ethanol. We conclude that the protective effect of intragastric TMA can be explained by its dose-related effect in enhancing gastric mucus secretion for TMA 1 and 10 mg/kg and the significantly greater increase in gastric juice volume for TMA 10 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1996

The effects of gamma-radiation on intestinal motor activity and faecal pellet expulsion in the guinea pig.

The effects of whole-body gamma-radiation (10 Gy) on intestinal motor activity was examined in the small and large intestine of the guinea pig 18 hr post irradiation. Neurally mediated relaxations of isolated gut bath preparations were generally unaffected. However, the contractile responses to direct smooth muscle stimulation with the cholinergic muscarinic agonist carbachol or ganglionic stimulation of intrinsic cholinergic motor neurones were significantly increased in the duodenum and colon but not the jejunum. This increased sensitivity to cholinergic stimulation was reflected in an increased contractility and a shift in the concentration-response curves for carbachol. The specificity of radiation actions for cholinergic mediated contractions was further supported by the observation that histamine-evoked contractions were unaffected. In a second series of experiments we examined the effects of gamma-radiation on the rate of pellet expulsion from freshly excised colons. Both colons from irradiated animals and nonirradiated colons exposed to carbachol showed significantly faster rates of pellet expulsion, indicative of increased propulsive motility. Pretreatment of animals with 0.5 mg/kg sc of the 5HT3 receptor antagonist Granisetron prevented the effect of radiation and reduced the pellet expulsion rate to below normal. These results indicate that gastrointestinal motility disturbances seen in organ-bath preparations of the intestine from rats exposed to whole-body gamma-radiation may be related to an increased sensitivity of the cholinergic muscarinic system.

Animals↗

PubMed1990

Autoimmune preganglionic sympathectomy induced by acetylcholinesterase antibodies.

Systemic injection of monoclonal antibodies to neural acetylcholinesterase in adult rats caused a syndrome with permanent, complement-mediated destruction of presynaptic fibers in sympathetic ganglia and adrenal medulla. Ptosis, hypotension, bradycardia, and postural syncope ensued. In sympathetic ganglia, acetylcholinesterase activity disappeared from neuropil but not from nerve cell bodies. Choline acetyltransferase activity and ultrastructurally defined synapses were also lost. Electrical stimulation of presynaptic fibers to the superior cervical ganglion ceased to evoke end-organ responses. On the other hand, direct ganglionic stimulation remained effective, and the postganglionic adrenergic system appeared intact. Motor performance and the choline acetyltransferase content of skeletal muscle were preserved, as was parasympathetic (vagal) function. This model of selective cholinergic autoimmunity represents another tool for autonomic physiology and may be relevant to the pathogenesis of human dysautonomias.

Acetylcholinesterase↗

PubMed2005

Penile erectile responses to electric stimulation are enhanced by a new phosphodiesterase type-5 inhibitor.

AIM: This study was conducted to investigate the effect of DA-8159, a new phosphodiesterase type-5 (PDE5) inhibitor, on electrostimulation-induced penile erection in rats. METHODS: Intracavernous pressure (ICP) and arterial blood pressure (BP) were simultaneously recorded through electric pelvic-ganglion stimulation (2-10 Hz) after the oral administration of DA-8159 (3 or 10 mg/kg) in normal and streptozotocin-induced diabetic rats. Statistical analysis was performed on the maximal intracavernous pressure (ICP), detumescence time, maximal intracavernous pressure/blood pressure (ICP/BP) ratio, and the area under the curve (AUC) of the ICP/BP ratio. RESULTS: In normal and diabetic rats, electrical stimulation of the pelvic ganglion induced a frequency- and dose-dependent increase in the intracavernous pressure. The ICP/BP ratio and the corresponding AUC values were also significantly and dose-dependently increased after DA-8159 administration. In addition, the detumescence time significantly increased after DA-8159 administration compared to that of the controls. CONCLUSIONS: These results show that the DA-8159 significantly increased the intracavernous pressure response and prolonged the decay period induced by electrical stimulation of the pelvic ganglion, and suggest that DA-8159 might be a potential therapeutic agent for the treatment of erectile dysfunction.

Animals↗