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Biomedical subjects

W C de Groat

Publications and source records attributed to W C de Groat.

At least 55 records · Page 3Linked to original sources
PubMed2000

Transneuronal labeling of neurons in the adult rat central nervous system following inoculation of pseudorabies virus into the colon.

Transneuronal tracing with pseudorabies virus (PRV) was used to identify sites in the central nervous system involved in the neural control of colon function. PRV-immunoreactive (IR) cells were primarily localized to the caudal lumbosacral (L6-S1) and caudal thoracicrostral lumbar (T13-L1) spinal segments with the distribution varying according to survival time (72-96 h). In the lumbosacral spinal cord at all time points examined, significantly (P < or = 0.005) greater numbers of PRV-IR cells were present in the region of the sacral parasympathetic nucleus (SPN) of the S1 spinal segment compared to that of the L6 segment. These studies also revealed morphologically distinct cell types with a differential distribution (probably interneurons and preganglionic parasympathetic neurons) in the region of the SPN in the L6-S1 spinal segments following colon inoculation. PRV-labeled neurons were located at various levels of the neuraxis and at many sites had a distribution similar to that following injection of virus to other urogenital organs. However, some unique sites in the dorsal motor nucleus of the vagus, nucleus of the solitary tract, nucleus ambiguus and area postrema were also identified. To determine if labeling in these caudal medullary sites was mediated by spinal or vagal pathways, the colon was inoculated with PRV in animals with a complete spinal cord (T8) transection (5-7 days prior). Following spinal transection, PRV-infected cells were detected in the same caudal medullary regions; however, labeling in other regions (e.g., Barrington's nucleus) was eliminated or significantly reduced. These studies have yielded several novel observations concerning the central neural control of colonic function: (1) the preganglionic efferent and primary afferent innervation of the colon arises primarily from the S1 spinal segment; (2) the distribution of PRV-infected neurons in the central nervous system following colon inoculation was similar to that following PRV inoculation of other urogenital organs; (3) Barrington's nucleus, which has been identified previously as the pontine micturition center, may have a role in colonic function; and (4) PRV infection in Barrington's nucleus following colon inoculation is mediated by bulbospinal pathways whereas labeling in caudal medullary regions is mediated, at least in part, by vagal pathways.

Animals↗
PubMed2000

Smooth muscle and parasympathetic nerve terminals in the rat urinary bladder have different subtypes of alpha(1) adrenoceptors.

Neurally evoked contractions and release of (3)H- acetylcholine (ACh) during electrical field stimulation were measured in rat urinary bladder strips. The alpha(1) agonist phenylephrine (PE, 2-8 microM) increased the amplitude of neurally evoked contractions, facilitated the release of ACh and increased the baseline tone of the bladder strips. The PE-induced facilitation of the contractions did not significantly change during a prolonged exposure to PE (120 min), whereas the PE-induced rise in baseline tone gradually decreased to 65% of the initial value. Low concentrations of specific alpha(1A) antagonists, 5-methyl urapidil (5-MU), REC15/2739 and WB-4101 competitively inhibited the facilitation of the neurally-evoked contractions (pA(2:) 8.77; 9.59 and 9.62, respectively), whereas higher concentrations of 5-MU (IC(50): 48 nM) were required to suppress the PE-rise in baseline. WB-4101 (100 microM) inhibited the PE-induced facilitation of ACh release. The irreversible alpha(1B) antagonist chloroethyl-clonidine (CEC, 10-50 microM) inhibited the PE-evoked rise in base line tone, but did not affect the PE-induced facilitation of the neurally evoked contractions nor the facilitation of ACh release. However, CEC increased the area and amplitude of the neurally-evoked contractions by 261+/-33 and 47.2+/-8.4%, respectively. Atropine significantly inhibited the CEC evoked increase in area and amplitude of the electrically evoked contractions (76.5+/-4.8 and 40.8+/-3%, respectively) indicating that CEC facilitated the cholinergic responses of the electrically stimulated bladder strips. It is concluded that alpha(1A) and CEC sensitive alpha(1B) and/or alpha(1D) adrenoceptors are expressed in the rat bladder in different locations. On the cholinergic nerve terminals alpha(1A) adrenoceptors mediate prejunctional facilitation, whereas postjunctional alpha(1B)/alpha(1D) adrenoceptors mediate smooth muscle contraction.

Acetylcholine↗
PubMed2000

Multimicroelectrode stimulation within the cat L6 spinal cord: influences of electrode combinations and stimulus interleave time on knee joint extension torque.

During multimicroelectrode stimulation within the cat L6 spinal cord, the number of electrodes activated, their separation distance, and the stimulus interleave time all influenced isometric knee joint extension torque. The torque evoked by stimulation with a three electrode combination could be enhanced or suppressed when compared with that evoked by single or paired electrode stimulation. A similar difference was noted when comparing two electrode combination versus single electrode stimulation. Relative fatigue was not improved significantly by interleaving the stimuli from two or three microelectrodes. Compared with the extension torque response evoked by noninterleaved stimulation, torque evoked by interleaved stimulation with the two microelectrode combination was decreased when the electrode distance was 2.0 mm or less and increased when the electrode distance was 3.0 mm. Designing an optimal stimulation strategy for multimicroelectrode spinal cord stimulation will be challenging and complex if a suppression effect among these electrodes is to be avoided. To reduce muscle fatigue, an asynchronous, interleaved strategy of stimulation may be required.

Animals↗
PubMed2000

Influence of temperature on activity of the isolated whole bladder preparation of neonatal and adult rats.

The temperature sensitivity of in vitro whole bladder preparations from neonatal and adult rats with or without chronic partial urethral obstruction was investigated. After the bladder was filled to a volume eliciting isovolumetric contractions, temperature was changed between 19 and 38 degrees C. In all preparations, higher temperatures were associated with higher frequencies of spontaneous intravesical pressure waves (IVPW). In 1- to 2-wk-old neonates, IVPW amplitude increased as the temperature increased; however, in older neonates and normal adults, the opposite occurred. The transition period was at 3 wk of age when bladder volume also markedly increased. At this age as well as in adult rats with outlet obstruction, changing temperature had little influence on the amplitude of IVPW. Thus obstructed outlet bladders and 3-wk-old bladders had similar properties. It is concluded that the properties of bladder muscle are changed during postnatal maturation and that in 3-wk-old rats, when brain control of voiding is emerging, micturition is abnormal, leading to obstructive changes in bladder muscle.

Aging↗
PubMed1999

Increased c-fos expression in spinal lumbosacral projection neurons and preganglionic neurons after irritation of the lower urinary tract in the rat.

Chemical irritation of the lower urinary tract (LUT) induces c-fos expression in neurons in the lumbosacral (L(6) and S(1)) spinal cord. This study used axonal tracing with fluorescent dyes to identify the types of spinal neurons expressing Fos immunoreactivity (IR) after LUT irritation in the rat. Fos-IR was detected in lateral and medial superficial dorsal horn, the sacral parasympathetic nucleus (SPN) and lamina X around the central canal. Fos-IR was detected in spinal neurons projecting to supraspinal sites (brainstem and hypothalamus), in preganglionic neurons (PGN) and in unlabeled segmental interneurons. A substantial percentage (20%) of dye labeled PGN exhibited Fos-IR after LUT irritation; and a larger percentage (36%) exhibited Fos-IR after electrical stimulation of the pelvic nerve which contains afferent pathways from all of the pelvic organs. The majority (average 55%) of Fos-positive neurons projecting to supraspinal sites were also located in the region of the SPN. A selective distribution of different types of neurons was detected in this region: PGN were located ventral to the spinal projection neurons which in turn were located ventral to the majority of unidentified Fos-positive neurons. The distribution of Fos-positive PGN and projection neurons was similar in spinal intact and spinal transected animals indicating that c-fos expression was mediated by monosynaptic afferent input or input from segmental interneurons and was not due to activation of supraspinal micturition reflex pathways.

Animals↗
PubMed1999

Increased excitability of afferent neurons innervating rat urinary bladder after chronic bladder inflammation.

The properties of bladder afferent neurons in L6 and S1 dorsal root ganglia of adult rats were evaluated after chronic bladder inflammation induced by 2 week treatment with cyclophosphamide (CYP; 75 mg/kg). Whole-cell patch-clamp recordings revealed that most (70%) of the dissociated bladder afferent neurons from control rats were capsaicin sensitive, with high-threshold long-duration action potentials that were not blocked by tetrodotoxin (TTX; 1 microM). These neurons exhibited membrane potential relaxations during voltage responses elicited by depolarizing current pulses and phasic firing during sustained membrane depolarization. After CYP treatment, a similar proportion (71%) of bladder afferent neurons were capsaicin sensitive with TTX-resistant spikes. However, the neurons were significantly larger in size (diameter 29.6 +/- 1.0 micrometer vs 23.6 +/- 0.8 micrometer in controls). TTX-resistant bladder afferent neurons from CYP-treated rats exhibited lower thresholds for spike activation (-25.4 +/- 0.5 mV) than those from control rats (-21.4 +/- 0.9 mV) and did not exhibit membrane potential relaxation during depolarization. Seventy percent of TTX-resistant bladder afferent neurons from CYP-treated rats exhibited tonic firing (average 12.3 +/- 1.4 spikes during a 500 msec depolarizing pulse) versus phasic firing (1.2 +/- 0.2 spikes) in normal bladder afferent neurons. Application of 4-aminopyridine (1 mM) to normal TTX-resistant bladder afferent neurons mimicked the changes in firing properties after CYP treatment. The peak density of an A-type K+ current (IA) during depolarizations to 0 mV in TTX-resistant bladder afferent neurons from CYP-treated rats was significantly smaller (42.9 pA/pF) than that from control rats (109.4 pA/pF), and the inactivation curve of the IA current was displaced to more hyperpolarized levels by approximately 15 mV after CYP treatment. These data suggest that chronic inflammation induces somal hypertrophy and increases the excitability of C-fiber bladder afferent neurons by suppressing IA channels. Similar electrical changes in sensory pathways may contribute to cystitis-induced pain and hyperactivity of the bladder.

4-Aminopyridine↗
PubMed1999

Influence of glutamate receptor antagonists on micturition in rats with spinal cord injury.

This study was undertaken to determine if an AMPA (LY215490) or an NMDA (MK-801) glutamatergic receptor antagonist can reduce urinary tract dysfunctions related to detrusor hyperreflexia and detrusor-sphincter dyssynergia in awake, spinal cord-injured (SCI) rats. Experiments were performed on female Sprague-Dawley rats in which the spinal cord was completely transected at T(8-10) level, 2-3 weeks prior to performing an intravesical continuous infusion cystometrogram (CMG). Bladder volume threshold (VT) for inducing voiding and voiding efficiency (VE) were determined by measuring voided volumes and residual volumes (RV). After control CMGs were performed, cumulative intravenous doses of LY215490 (0.1, 1, and 10 mg/kg) or MK-801 (0.03, 0.3, and 3 mg/kg) were administered at 120-min intervals. Small doses of LY215490 (0.1 mg/kg) or MK-801 (0. 03 and 0.3 mg/kg) did not affect any parameters. A large dose (10 mg/kg) of LY215490 decreased maximal voiding pressure (MVP) by 27% and increased RV by 119% and VT by 58% but did not decrease VE. The highest cumulative dose (3 mg/kg) of MK-801 significantly increased RV by 134% and VT by 44% and markedly decreased VE by 60% and MVP by 18%. The effects of LY215490 to reduce MVP and increase VT without changing VE suggest that an AMPA receptor antagonist might be useful in treating detrusor-sphincter dyssynergia and bladder hypertrophy after SCI. The effect of MK-801 to markedly reduce VE indicates that NMDA receptor antagonists may exacerbate neurogenic bladder dysfunction in SCI patients.

Animals↗
PubMed1999

Maturation of bladder reflex pathways during postnatal development.

Neuroanatomical and electrophysiological techniques have provided new insights into the organization of the spinal cord circuitry and the neurotransmitter mechanisms involved in primitive voiding reflexes in neonatal animals. In addition, studies of unitary synaptic transmission in spinal cord slice preparations indicate that developmental and spinal cord injury induced plasticity in sacral parasympathetic reflex pathways is due in part to alterations in glutamatergic excitatory transmission between interneurons and parasympathetic preganglionic neurons. It is proposed that these synaptic changes are due to competition between segmental and supraspinal inputs. Thus synaptic remodeling in the sacral parasympathetic nucleus is likely to be an important factor in the postnatal maturation of voiding reflexes.

Aging↗
PubMed1999

Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis.

PURPOSE: This study was conducted to examine effects of nitric oxide (NO) donors on bladder hyperactivity induced by cyclophosphamide (CYP)-induced cystitis. MATERIALS AND METHODS: Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (100 mg./kg.), and then their micturition pattern including mean micturition volume and the number of micturitions during 24 hours was recorded in a metabolic cage before and after CYP treatment. Forty-eight hours after CYP injection, bladder function under urethane anesthesia was evaluated by cystometry with continuous saline infusion (0.04 ml. per minute) or under isovolumetric conditions (0.8 ml. bladder volume). NO donors, S-nitroso-N-acetyl-penicillamine (SNAP, 2 mM) or sodium nitroprusside (SNP, 1 mM), and an NO synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 20 mM) were administered intravesically. Direct action of SNAP on bladder afferent neurons was also tested in a patch-clamp recording study. RESULTS: The number of micturitions significantly increased during the first 24 hours after CYP injection (19.0 +/- 0.88 versus 92.1 +/- 16.3 micturitions/24 hours, mean +/- SE, n = 25) (p <0.001). There was no significant difference in total micturition volume before (12.3 +/- 1.0 ml./24 hours) and after CYP treatment (15.6 +/- 1.5 ml./24 hours). During continuous infusion cystometry, intercontraction interval (ICI) was smaller in CYP-injected rats than in control rats. In CYP-injected animals, NO donors increased the ICI, but did not change the amplitude of bladder contractions. Continuous intravesical infusion of the NOS inhibitor did not alter the cystometric parameters. During cystometry under isovolumetric conditions, contraction frequency was decreased after NO donor administration. NO donors did not influence bladder activity in control rats. In patch clamp recordings, when SNAP (500 microM) was directly applied to dissociated afferent neurons innervating the urinary bladder, high-voltage-activated Ca2+ channel currents were suppressed by approximately 30%. CONCLUSIONS: Intravesical NO donors can suppress CYP-induced bladder hyperactivity. We hypothesize that the effect of NO donors is not due to smooth muscle relaxation, but rather due to an inhibitory effect on bladder afferent pathways that was manifested by an increase in intercontraction interval without changes in contraction amplitude. NO donors may be considered as a possible treatment of CYP-induced and other types of bladder inflammation.

Administration, Intravesical↗
PubMed1999

Function, signal transduction mechanisms and plasticity of presynaptic muscarinic receptors in the urinary bladder.

Presynaptic M1 muscarinic receptors on parasympathetic nerve terminals in rat urinary bladder strips are involved in an autofacilitatory mechanism that markedly enhances acetylcholine release during continuous electrical field stimulation. The facilitatory muscarinic mechanism is dependent upon a PKC mediated second messenger pathway and influx of extracellular Ca2+ into the parasympathetic nerve terminals via L and N-type Ca2+ channels. Prejunctional muscarinic facilitation has also been detected in human bladders. The muscarinic facilitatory mechanism is upregulated in hyperactive bladders from chronic spinal cord transected rats; and the facilitation in these preparations is primarily mediated by M3 muscarinic receptors. Presynaptic muscarinic receptors represent a new target for pharmacological treatment of bladder hyperactivity. If presynaptic facilitation is restricted to the bladder and not present in other tissues then drugs acting at this site might be expected to exhibit uroselectivity.

Acetylcholine↗
PubMed1999

Changes in micturition after spinal cord injury in conscious rats.

OBJECTIVES: To determine the feasibility of urodynamic monitoring of voiding function in conscious, female spinal cord-injured (SCI) rats and to compare the voiding function in SCI rats and those with normal spinal cord (NSC). METHODS: Cystometrograms were performed on conscious, female Sprague-Dawley rats. Parameters measured included voided volume, residual volume, volume threshold for inducing micturition, voiding efficiency, micturition pressure, pressure threshold for inducing micturition, and bladder contraction duration. SCI animals were studied 2 to 3 weeks after T8-T10 spinal cord transection. RESULTS: Approximately one half of SCI rats exhibited uninhibited bladder contractions before voiding. These contractions were not observed in NSC rats. Compared with NSC rats, SCI rats had larger volume thresholds (1.43 versus 0.34 mL, P <0.001) and voided volumes (0.72 versus 0.31 mL, P <0.01). Although SCI rats had larger micturition pressures (65 versus 35 cm H2O, P <0.001), residual volumes were increased (0.71 versus 0.03 mL, P <0.001) and voiding efficiency was decreased (50% versus 92%, P <0.001) compared with the measurements in NSC rats. The micturition pressure threshold was slightly lower (23%, P <0.05) and the bladder contraction duration was longer (33%, P <0.05) in SCI rats than in NSC rats. CONCLUSIONS: Cystometric studies in conscious female SCI and NSC rats revealed significant changes in the activity of the lower urinary tract after spinal cord transection. Fifty-five percent of SCI rats exhibited detrusor hyperreflexia during bladder filling and decreased voiding efficiency compared with NSC animals. This method of cystometric evaluation in the conscious animal is likely to be useful for evaluating new pharmacologic treatments for neurogenic bladder dysfunction.

Animals↗
PubMed1999

Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder.

PURPOSE: Pharmacological treatment of the overactive bladder relies on partially blocking the efferent parasympathetic innervation to the detrusor with anticholinergic drugs. However, often these drugs have troublesome side effects and doses are insufficient to restore continence in patients with detrusor instability. We present the background, basic and clinical research with intravesical instillation of capsaicin and resiniferatoxin as treatments for the overactive bladder. MATERIALS AND METHODS: Capsaicin, the main pungent ingredient in hot peppers of the genus Capsicum, is a specific neurotoxin that desensitizes C fiber afferent neurons which may be responsible for signals that trigger detrusor overactivity. RESULTS: In the last 6 years studies have demonstrated encouraging improvement in lower urinary tract symptoms with minimal long-term complications. Most of these studies have also demonstrated that the acute pain and irritation associated with capsaicin are major deterrents to widespread use. Therefore, resiniferatoxin, an ultra-potent analogue of capsaicin which appears to have similar efficacy but less acute side effects, may be more useful. CONCLUSIONS: Intravesical capsaicin and resiniferatoxin are novel and promising treatments for the overactive bladder, with profound basic and clinical implications.

Administration, Intravesical↗
PubMed1999

"Skin-CNS-bladder" reflex pathway for micturition after spinal cord injury and its underlying mechanisms.

PURPOSE: A "skin-CNS-bladder" reflex pathway for inducing micturition after spinal cord injury has been established in cat. This reflex pathway which is basically a somatic reflex arc with a modified efferent limb that passes somatic motor impulses to the bladder, has been designed to allow spinal cord injured patients to initiate voiding by scratching the skin. MATERIALS AND METHODS: The skin-CNS-bladder reflex was established in the cat by intradural microanastomosis of the left L7 ventral root (VR) to the S1 VR while leaving the L7 dorsal root (DR) intact to conduct cutaneous afferent signals that can trigger the new micturition reflex arc. After allowing 11 weeks for axonal regeneration, urodynamic, pharmacological and electrophysiological studies were conducted in pentobarbital or chloralose anesthetized animals. RESULTS: A detrusor contraction was initiated at short latency by scratching the skin or by percutaneous electrical stimulation in the L7 dermatome. Maximal bladder pressures during this stimulation were similar to those activated by bladder distension in control animals. Electrophysiological recording revealed that single stimuli (0.3 to 3 mA, 0.02 to 0.2 msec duration) to the left L7 spinal nerve in which the efferent axons had degenerated evoked action potentials (0.5 to 1 mV) in the left S1 spinal nerve distal to the anastomosis. In addition, increases in bladder pressure were elicited by trains of the stimuli (5 to 20 Hz, 5 seconds) applied to the L7 spinal nerve. Urodynamic studies including external sphincter EMG recording demonstrated that the new reflex pathway could initiate voiding without detrusor-external urethral sphincter dyssynergia. Atropine (0.05 mg./kg., i.v.) or trimethaphan (5 mg./kg., i.v.), a ganglionic blocking agent, depressed the bladder contractions elicited by skin stimulation. The skin-CNS-bladder reflex could also be elicited after transecting the spinal cord at the L2-L3 or L7-S1 levels. CONCLUSION: The cross-wired somato-autonomic bladder reflex is effective in initiating bladder contractions and coordinated voiding in cats with an intact neuraxis and can also induce bladder contractions after acute transection of the lumbar spinal cord. The new pathway is mediated by cholinergic transmission involving both nicotinic and muscarinic receptors. It is concluded that somatic motor axons can innervate bladder parasympathetic ganglion cells and thereby transfer somatic reflex activity to the bladder smooth muscle.

Anastomosis, Surgical↗
PubMed1999

Isometric torque about the knee joint generated by microstimulation of the cat L6 spinal cord.

Isometric torque was generated about the knee joint by microstimulation of the cat L6 spinal cord using a single microelectrode. The torque responses varied with microstimulation location. Appreciable extension torque was generated by microstimulation in ventrolateral locations of the L6 spinal cord. Stimulation parameters (intensity, frequency and pulse-width) also influenced the extension torque. Specific stimulation parameters (100 microA intensity, 40 Hz frequency and 0.20 ms pulse-width) appear best suited for mapping the spinal cord based on knee joint torque responses. Low levels of cocontraction of the extensor and flexor could be achieved when extension torque was produced, but also varied with the stimulation locations. There are locations in the L6 ventral horn where microstimulation could evoke sustained extension for at least 4 min with only a slight change in torque. This study suggests the possibility of restoring lower limb function in patients with spinal cord injury above the lumbar level.

Animals↗
PubMed1999

Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery occlusion.

The contribution of glutamatergic and dopaminergic mechanisms to bladder hyperactivity after left middle cerebral artery occlusion was evaluated by determining the effects of intravenous cumulative doses of an N-methyl-D-aspartate (NMDA) glutamatergic antagonist (MK-801) and D1-selective (Sch-23390), D2-selective (sulpiride), or nonselective (haloperidol) dopaminergic antagonists on bladder activity in sham-operated (SO) and cerebral-infarcted (CI) rats. MK-801 (1 and 10 mg/kg) or sulpiride (3-30 mg/kg) significantly increased bladder capacity (BC) in CI but decreased or had no effect, respectively, on BC in SO. Sch-23390 (0.1-3 mg/kg) decreased BC in both SO and CI. In both CI and SO, low doses of haloperidol (0.1-1 mg/kg) increased BC, but a higher dose (3 mg/kg) reversed this effect. Administration of haloperidol (0.3 mg/kg) or sulpiride (10 mg/kg) in combination with MK-801 (0.01-10 mg/kg) markedly increased BC in CI but produced small decreases or increases in BC depending on the dose of MK-801 in SO. These results indicate that the bladder hyperactivity induced by cerebral infarction is mediated in part by NMDA glutamatergic and D2 dopaminergic excitatory mechanisms.

Animals↗
PubMed1999

Effect of capsaicin on the micturition reflex in normal and chronic spinal cord-injured cats.

The effect of capsaicin (10-80 mg/kg sc) on reflex activity of the urinary bladder was examined in anesthetized normal as well as anesthetized and awake chronic spinal cord-injured (SCI) cats. In normal cats, capsaicin elicited a transient increase in the frequency of isovolumetric bladder contractions and reduced the volume threshold for inducing micturition, but did not depress the amplitude of bladder contractions or the reflex firing on bladder nerves. In anesthetized SCI cats, capsaicin depressed reflex bladder activity and firing on bladder nerves. In awake SCI cats, capsaicin initially decreased the volume threshold for inducing micturition; however, after a delay of 3-6 h the volume threshold increased and intravesical voiding pressure decreased. This effect persisted for 4-12 days. It is concluded that capsaicin-sensitive C fiber bladder afferents are not involved in initiating reflex micturition in normal cats, but play an essential role in triggering automatic micturition in chronic SCI cats. The results are consistent with the clinical data indicating that C fiber bladder afferents contribute to bladder hyperactivity and incontinence in patients with neurogenic bladder dysfunction.

Animals↗
PubMed1999

Modulation of voiding and storage reflexes by activation of alpha1-adrenoceptors.

OBJECTIVE: This paper reviews recent studies in animals that examined the effect on lower urinary tract function of alpha1-adrenoceptor agonists and antagonists. METHODS: Bladder reflexes were studied in vivo on anesthetized rats and cats using cystometrographic and electrophysiologic techniques. Neurally-evoked bladder contractions and release of acetylcholine (ACh) were also studied in rat bladder strips in vitro. RESULTS: Administration of the alpha1-adrenoceptor agonist, phenylephrine (PE) to isolated strips of rat bladder enhanced neurally-evoked bladder contractions and increased basal tone. The former effects of PE were blocked by a selective alpha1A antagonist and the latter by an alpha1B antagonist. Activation of alpha1A receptors by PE enhanced ACh release evoked by electrical field stimulation in bladder strips. PE also enhanced transmission in cat bladder ganglia. PE or noradrenaline act on alpha- and beta-adrenoceptors on urothelial cells to release nitric oxide. It is concluded that facilitatory alpha1A-adrenoceptors are located prejunctionally in the bladder, whereas alpha1B adrenoceptors are located postjunctionally. In the central nervous system of the rat and cat facilitatory alpha1-adrenergic mechanisms can modulate the sympathetic, parasympathetic and somatic outflow to the urinary tract. In addition inhibitory alpha1 adrenoceptor mechanisms have been detected in the rat spinal cord. Activation of these receptors with PE raises the intravesical pressure threshold for inducing micturition and decreases voiding frequency. CONCLUSIONS: alpha1-adrenoceptors are located at various sites in the bladder and in the neural pathways controlling lower urinary tract function. At most sites these receptors mediate facilitatory responses that enhance smooth muscle activity or facilitate storage or voiding reflexes. However, alpha1-adrenoceptor inhibitory mechanisms in the rat spinal cord, can also reduce the frequency of voiding reflexes. This effect is possibly mediated by an inhibition in the afferent limb of the micturition reflex pathway.

Adrenergic alpha-Agonists↗