Relaxation mechanisms induced by stimulation of nerves and by nitric oxide in sheep urethral muscle.

Garcia-Pascual, Angeles; Triguero, Domingo

doi:10.1113/jphysiol.1994.sp020135

Cited by 35 publications

(39 citation statements)

References 37 publications

(38 reference statements)

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“…This observation supports the above view, since oxyhaemoglobin evokes its inhibitory action by binding NO-directly to form a nitrosyl-haemoprotein complex which prevents the diffusion of NO-from nerve terminals to smooth muscle cells (Martin, Villani, Jothianandan & Furchgott, 1985). Furthermore, Methylene Blue which has previously been proposed as a specific inhibitor of soluble guanylate cyclase (Martin et al 1985), has recently been suggested to inactivate NO-by generation of the superoxide anion (02-) (Garcia-Pascual & Triguero, 1994). It has been shown that a reduced form of Methylene Blue can generate the superoxide anion by auto-oxidation in the presence of oxygen (MacCord & Fridorich, 1970) and that NO-can be inactivated by the superoxide anion (Palmer, Ferrige & Moncada, 1987 (Fig.…”

Section: Discussionmentioning

confidence: 99%

The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway.

Tanaka

Liang

Takahashi

et al. 1996

The Journal of Physiology

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1. To study the possible role of nitric oxide (NO free radical; NO-) or NO-containing compounds in the non-adrenergic, non-cholinergic (NANC) relaxations, we observed the effects of carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO; a newly synthesized NO scavenger) on NANC relaxations in the cat airway. In addition, we also observed the effects of C-PTIO on excitatory junction potentials (EJPs), since NO-has a prejunctional action on transmitter release. 4. After pretreatment of the bronchial tissues with a-chymotrypsin (1 unit ml-') for 30 min in order to inhibit any response to peptides, EFS evoked monophasic NANC relaxation.C-PTIO (10--10-4 M) dose-dependently suppressed, and at a concentration of 10-4 M almost halved, the amplitude of NANC relaxation. Additional application of L-NAME further reduced the C-PTIO-resistant NANC relaxation to 20-30 % of the initial value. 5. C-PTIO (10-4 M) enhanced the EJP amplitude evoked by single EFS in the trachea but not in the bronchi. However, C-PTIO enhanced the summation of the EJPs to repeated stimulation to a similar extent in the tracheal and bronchial tissues. Simultaneous application of C-PTIO and L-NAME did not further enhance the summation. 6. These results indicate that NO-and NO-containing compounds are involved in the L-NAME-sensitive NANC relaxation in the cat airway, and that only NO-has a prejunctional action which inhibits excitatory neuroeffector transmission.We reported that at least two neurotransmitters, possibly NO or NO-containing compounds and a peptide such as vasoactive intestinal polypeptide (VIP), are involved in the inhibitory non-adrenergic, non-cholinergic (NANC) neurotransmission in the cat airway and that the distribution profile of the two components differs in the central and peripheral airways (Jing, Inoue, Tashiro, Takahashi & Ito, 1995;Takahashi, Tanaka, Abdullah, Jing, Inoue & Ito, 1995 .

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Section: Discussionmentioning

confidence: 99%

The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway.

Tanaka

Liang

Takahashi

et al. 1996

The Journal of Physiology

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“…The fact that NC effectively induced cyclic GMP accumulation in oviductal vascular preparations argues against MB being a specific inhibitor of soluble guanylate cyclase as is generally assumed. Generation of 02-, which induces direct chemical inactivation of extracellular NO has been shown to mediate the inhibition of NO-dependent relaxations by MB in some tissues (Wolin et al, 1990;Garcia-Pascual & Triguero, 1994). Nitrosothiols, such as NC can yield NO directly to the cytoplasm of smooth muscle cells following denitrosation at the membrane (Kowaluk & Fung, 1990), being less sensitive to extracellular inactivation by 02-.…”

Section: I1-mentioning

confidence: 99%

“…The analytical procedure followed is described elsewhere (Garcia-Pascual & Triguero, 1994) with minor modifications. In brief, vessel segments were quickly plunged into liquid nitrogen and stored at -70'C.…”

Section: Determination Of Cyclic Gmp Levelsmentioning

confidence: 99%

Endothelium‐dependent relaxation to acetylcholine in bovine oviductal arteries: mediation by nitric oxide and changes in apamin‐sensitive K⁺ conductance

Garcia-Pascual

Labadía

Jiménez

et al. 1995

British J Pharmacology

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1 Mechamisms underlying the relaxant response to acetylcholine (ACh) were examined in bovine oviductal arteries (o.d. 300-500 pm and i.d. 150-300 pm) in vitro. Vascular rings were treated with indomethacin (10 pM) to prevent the effects of prostaglandins. 2 ACh elicited a concentration-related relaxation in ring segments precontracted with noradrenaline (NA), which was abolished by endothelium denudation. 3 The ACh-induced relaxation was attenuated but not abolished by NG-nitro-L-arginine (L-NOARG, 1 gM-1 mM), an inhibitor of nitric oxide (NO) formation. The inhibition caused by L-NOARG (10 pM) was reversed by addition of excess of L-arginine but not D-arginine (1 mM). 4 In high K+ (40-60 mM)-contracted rings, ACh was a much less effective vasodilator and its relaxant response was completely abolished by L-NOARG (100 pM).5 In NA (10 gM)-contracted rings, ACh induced sustained and concentration-dependent increases in cyclic GMP, which were reduced below basal values by L-NOARG (100 pM), while potent relaxation persisted. Similar increases in cyclic GMP were evoked by ACh in high K+ (50 mM)-treated arteries and under these conditions, both cyclic GMP accumulation and relaxation were L-NOARG-sensitive. 6 S-nitroso-L-cysteine (NC), a proposed endogenous precursor of endothelial NO, also induced cyclic GMP accumulation in NA-contracted oviductal arteries. 7 Methylene blue (MB, 10 pM), a proposed inhibitor of soluble guanylate cyclase, inhibited both endothelium-dependent relaxation to ACh and endothelium-independent response to exogenous NO, whereas relaxation to NC remained unaffected. 8 The L-NOARG-resistant response to ACh was not affected by either ouabain (0.5 mM), glibenclamide (3 pM), tetraethylammonium (TEA, 1 mM) or charybdotoxin (50 nM), but was selectively blocked by apamin (0.1-1 pM). However, apamin did not inhibit either relaxation to ACh in high K+-contracted rings or endothelium-independent relaxation to either NO or NC. 9 Apamin and MB inhibited ACh-induced relaxation in an additive fashion, suggesting the involvement of two separate modulating mechanisms. 10 These results suggest that ACh relaxes bovine oviductal arteries by the release of two distinct endothelial factors: a NO-like substance derived from L-arginine, which induces cyclic GMP accumulation in smooth muscle, and another non-prostanoid factor acting by hyperpolarization mechanisms through alterations in apamin-sensitive K+ conductance.

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“…A rich supply of nitrergic nerves has been identified by NADPH-diaphorase histochemistry and nitric oxide synthase (NOS) immunohistochemistry in the outflow region (urethra, bladder neck and bladder base or trigone) of several species including rat (McNeill et al, 1992), pig (Persson et al, 1993), sheep (Triguero et al, 1993) and human (Smet et al, 1994a;Leone et al, 1994). Furthermore, functional studies have demonstrated that isolated urethral and trigonal smooth muscles in all the species studied so far, respond to electrical field stimulation (EFS) with pronounced NANC relaxations, which can be blocked by NO synthesis inhibitors and mimicked by NO and NO donors (Garcia-Pascual et al, 1991;Andersson et al, 1991;Persson et al, 1992;1993;Garcia-Pascual & Triguero, 1994). This suggests that NO, or a related compound, is the relaxant mediator, which acts by increasing guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in smooth muscle (Garcia-Pascual & Triguero, 1994;Dokita et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, functional studies have demonstrated that isolated urethral and trigonal smooth muscles in all the species studied so far, respond to electrical field stimulation (EFS) with pronounced NANC relaxations, which can be blocked by NO synthesis inhibitors and mimicked by NO and NO donors (Garcia-Pascual et al, 1991;Andersson et al, 1991;Persson et al, 1992;1993;Garcia-Pascual & Triguero, 1994). This suggests that NO, or a related compound, is the relaxant mediator, which acts by increasing guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in smooth muscle (Garcia-Pascual & Triguero, 1994;Dokita et al, 1994). Moreover, an increase in both nitrite and nitrate, the metabolites of NO, has been measured in human urethral preparations upon EFS, which was inhibited by N0-nitro-L-arginine methyl ester (L-NAME) (Leone et al, 1994).…”

mentioning

confidence: 99%

Characterization of nitric oxide synthase activity in sheep urinary tract: functional implications

Garcia-Pascual

Costa

Labadía

et al. 1996

British J Pharmacology

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1 To define further the role of nitric oxide (NO) in urinary tract function, we have measured the presence of nitric oxide synthase (NOS) activity, and its relationship with functional NO-mediated responses to electrical field stimulation (EFS) in the urethra, the detrusor and the ureter from sheep. NOS activity was assayed by the conversion of L-['4C]-arginine to L-['4C]-citrulline. Endogenous production of citrulline was confirmed by thin layer chromatography. 2 NOS enzymatic activity was detected in the cytosolic fraction from tissue homogenates with the following regional distribution (pmol citrulline mg-' protein min-'): urethra (33 + 3.3), detrusor (13.1 + 1.1) and ureter (1.5 + 0.2). No activity was detected in the particulate fraction of any region. 3 NOS activity was dependent on Ca2+-calmodulin and required exogenously added NADPH and tetrahydrobyopterin (BH4) for maximal activity. Exclusion of calmodulin from the incubation mixture did not modify NOS activity, but it was significantly reduced in the presence of the calmodulin antagonist, calmidazolium, suggesting the presence of enough endogenous calmodulin to sustain the observed NOS activity. 4 NOS activity was inhibited to a greater extent by NG-nitro-L-arginine (L-NOARG) and its methyl ester (L-NAME) than by NG-monomethyl-L-arginine (L-NMMA), while 7-nitroindazole (7-NI) was a weak inhibitor and L-cannavine had no effect. 5 Citrulline formation could be inhibited by superoxide dismutase in an oxyhaemoglobin-sensitive manner, suggesting feedback inhibition of NOS by NO. 6 EFS induced prominent NO-mediated relaxations in the urethra while minor or no responses were observed in the detrusor and the ureter, respectively. Urethral relaxations to EFS were inhibited by NOS inhibitors with the rank order of potency: L-NOARG = L-NAME>7-NI> L-NMMA. 7In conclusion, we have demonstrated the presence of NO-synthesizing enzymatic activity in the sheep urinary tract which shows similar characteristics to the constitutive NOS isoform found in brain. We suggest that the enzymatic activity measured in the urethral muscle layer may account for the NOmediated urethral relaxation during micturition whereas regulation of detrusor and ureteral motor function by NOS containing nerves is less likely. Keywords: Nitric oxide; nitric oxide synthase; urethra; detrusor; ureter; nitrergic relaxation; urinary tract Introduction It has been suggested that nitric oxide (NO) has important regulatory functions in the urinary tract acting as a nonadrenergic, non-cholinergic (NANC)-relaxant transmitter. Specially relevant is the proposed role of NO in mediating the decrease in outlet resistance which accompanies micturition (Andersson, 1993). A rich supply of nitrergic nerves has been identified by NADPH-diaphorase histochemistry and nitric oxide synthase (NOS) immunohistochemistry in the outflow region (urethra, bladder neck and bladder base or trigone) of several species including rat (McNeill et al., 1992), pig (Persson et al., 1993), sheep (Triguero et al., 1993 and human (Sme...

show abstract

Relaxation mechanisms induced by stimulation of nerves and by nitric oxide in sheep urethral muscle.

Cited by 35 publications

References 37 publications

The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway.

The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway.

Endothelium‐dependent relaxation to acetylcholine in bovine oviductal arteries: mediation by nitric oxide and changes in apamin‐sensitive K⁺ conductance

Characterization of nitric oxide synthase activity in sheep urinary tract: functional implications

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Relaxation mechanisms induced by stimulation of nerves and by nitric oxide in sheep urethral muscle.

Cited by 35 publications

References 37 publications

The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway.

The possible role of nitric oxide in relaxations and excitatory neuroeffector transmission in the cat airway.

Endothelium‐dependent relaxation to acetylcholine in bovine oviductal arteries: mediation by nitric oxide and changes in apamin‐sensitive K+ conductance

Characterization of nitric oxide synthase activity in sheep urinary tract: functional implications

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Endothelium‐dependent relaxation to acetylcholine in bovine oviductal arteries: mediation by nitric oxide and changes in apamin‐sensitive K⁺ conductance