UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main objective of this work was to study the role of potassium channels in the cholinergic relaxation of cutaneous arteries during cooling. Acetylcholine (10(-8)-10(-4) M) produced isometric concentration-dependent relaxation of precontracted segments of rabbit ear (cutaneous) and femoral (noncutaneous) arteries; this relaxation was higher at 24 degrees C (cooling) than at 37 degrees C in ear, but not in femoral, arteries. In both types of arteries, at 37 and 24 degrees C, the relaxation to acetylcholine was partially reduced by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), and the relaxation that remained after L-NAME was higher at 24 degrees C than at 37 degrees C in ear, but not in femoral, arteries. At 37 and 24 degrees C, the persistent relaxation to acetylcholine after L-NAME was further reduced by smooth muscle depolarization with medium containing a high concentration of potassium (6 x 10(-2) M), and with the nonspecific inhibitors of potassium channels tetraethylammonium (10(-2) M) or 4-aminopyridine (5 x 10(-3) M) in both ear and femoral arteries. In ear arteries, the inhibitor of high conductance calcium-activated potassium channels charybdotoxin (10(-7) M), alone or combined with L-NAME, reduced the relaxation to acetylcholine at 24 degrees C, but not at 37 degrees C. In femoral arteries, charybdotoxin alone did not modify, but combined with L-NAME reduced, the relaxation to acetylcholine at either temperature. At 37 and 24 degrees C, the inhibitor of low conductance calcium-activated potassium channels apamin (10(-7) M), the inhibitor of ATP-dependent potassium channels glibenclamide (10(-5) M) and the cyclooxygenase inhibitor meclofenamate (10(-5) M), alone or combined with L-NAME, did not modify the relaxation of both ear and femoral arteries to acetylcholine. These results suggest: (1) the cholinergic relaxation of cutaneous (ear) and noncutaneous (femoral) arteries could be mediated by endothelial nitric oxide and by activation of potassium channels, and (2) cooling increases the relaxation of cutaneous arteries to cholinergic stimulation, which may be mediated, in part, by an increased response of potassium channels.
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PMID:Role of nitric oxide and potassium channels in the cholinergic relaxation of rabbit ear and femoral arteries: effects of cooling. 856 11

Smooth muscle cells distributed in the visceral organs are under the control of the autonomic nervous system, and contraction or relaxation of the muscle cells plays an important physiological role in the control of blood pressure, motility of the digestive, respiratory and urinary tracts and secretion. Recent physiological, pharmacological and histochemical investigations indicate that neurotransmitters other than acetylcholine or noradrenaline are involved in peripheral autonomic neuro-effector transmission, and these neurotransmitters are generally termed non-adrenergic, non-cholinergic (NANC) neurotransmitters. The neurotransmitters responsible for excitatory and inhibitory NANC neurotransmission (e-NANC and i-NANC respectively) have not been conclusively identified, but ATP, nitric oxide (NO) and peptides such as VIP and substance P are candidates for these roles. In this review, we discuss the possible role of ATP and NO as e- or i-NANC neurotransmitter in the digestive, respiratory and urinary tracts. Much of the work on NANC innervation in the digestive tract has been carried out on the circular muscle layers of the ileum. This receives inhibitory NANC innervation with ATP responsible for fast relaxation and VIP, and possibly NO, for the slow response. Early and late excitatory junction potentials can be recorded in the presence of atropine. The second is due to substance P since it is blocked in the presence of spantide and by desensitization of the tissue with high doses of substance P. The transmitter responsible for the early NANC contraction has not been identified. Electrical field stimulation (EFS) applied to the tracheal smooth muscle during contraction induced by 5-HT in the presence of atropine and guanethidine elicited monophasic NANC relaxation. By contrast, NANC relaxation elicited in the smaller airways was biphasic, comprising an initial fast component followed by a second slow one. L-NAME selectively abolished the first component without affecting the second. VIP-antagonists or alpha-chymotrypsin considerably attenuated the amplitude of the L-NAME insensitive relaxation. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission in the airway. In the urinary bladder a large, transient atropine resistant contraction occurs in response to pelvic nerve stimulation. This is blocked by alpha, beta methylene ATP suggesting that it is due to ATP. There is no evidence of inhibitory innervation. In the urethra contraction is completely blocked by atropine and guanethidine; a rapid NANC relaxation is abolished by drugs that block NO synthesis. Nerves containing peptides supply both urethra and bladder and may also be involved. These results suggest that all visceral smooth muscles may receive inhibitory NANC innervation involving NO. ATP produces contraction of the urinary bladder but relaxation of the digestive tract. The role of peptides is not yet clear but there is evidence that substance P may be an excitatory transmitter and VIP an inhibitory transmitter in many organs.
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PMID:[The control of smooth muscle tissues by nonadrenergic noncholinergic (NANC) nerve fibres in the autonomic nervous system]. 856 58

In the present study, we investigated if the relaxant effects of phosphodiesterase (PDE) III inhibitors on human vessels could be inhibited by a nitric oxide synthase blocker, L-NAME, or by a blocker of ATP-sensitive potassium channels (KATP), glibenclamide. The experiments were performed using an isometric myograph in isolated human s.c. small arteries obtained from healthy donors. After a priming procedure consisting of exposure to high potassium (120 mmol litre-1) solutions, phenylephrine 10 mumol litre-1 and an equilibrium period of 30 min, the preparations were contracted with a thromboxane A2 mimetic agent, U46619 1 mumol litre-1. Subsequently, cumulative concentration-response curves were constructed for the selective PDE III inhibitors amrinone, milrinone and enoximone, and for theophylline and dipyridamole, with and without the addition of L-NAME 100 mumol litre-1 or glibenclamide 1 mumol litre-1. Addition of L-NAME to the organ bath resulted in significantly higher pEC50 values (-log of the concentration required for 50% relaxation) for milrinone compared with the control: 2.77 (SEM 0.24) mol litre-1 (n = 5) vs 3.49 (0.17) mol litre-1 (n = 7) (P < 0.05). There was no significant difference between any other group. From our data we conclude that the relaxant properties of amrinone, enoximone, theophylline and dipyridamole are not dependent on nitric oxide release or on interaction with KATP channels. However, the effect of milrinone may be partly endothelium-dependent in human vessels in vitro.
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PMID:Effect of phosphodiesterase inhibitors on human arteries in vitro. 867 53

1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.
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PMID:Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase. 871 9

1. The effects of pregnancy on mesenteric arterial function were examined in constantly perfused (5 ml min-1) mesenteric arterial beds isolated from 21-day pregnant rats. The function of sympathetic and sensory-motor perivascular nerves, endothelium and smooth muscle was examined. The role of nitric oxide and prostaglandins in vasoconstrictor function was tested by use of NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) and indomethacin (10 microM), respectively. 2. Electrical field stimulation (EFS; 4-32 Hz, 1 ms, 90V, 30s) at basal tone elicited frequency-dependent vasoconstriction which was markedly reduced in preparations from pregnant rats at all frequencies. Vasoconstrictor responses to vasopressin and endothelin were also reduced in pregnancy and there was a trend towards a reduction in maximal responses to noradrenaline (NA). In contrast, there was no difference in vasoconstrictor responses to ATP, 5-hydroxytryptamine (5-HT) or angiotension II. 3. L-NAME (100 microM) augmented responses to EFS, NA, ATP and vasopressin in control mesenteric arterial preparations. In contrast, L-NAME augmented responses only to EFS in pregnancy, having no significant effect on responses to NA, ATP and vasopressin. 4. Indomethacin (10 microM) attenuated responses to NA and vasopressin, but not to EFS, in controls and in pregnancy. Responses to ATP were attenuated by indomethacin in controls but not in pregnancy. 5. Mesenteric preparations from pregnant rats were resistant to having tone raised by continuous perfusion with methoxamine. Despite an approximately 10 fold greater concentration of methoxamine, there was a significantly smaller increase in tone in preparations from pregnant, 34.27 +/- 4.8 mmHg (n = 11) compared to control, 65.92 +/- 5.4 mmHg (n = 11), rats. EFS (4-12 Hz, 60 V, 0.1 ms, 30s) in the presence of guanethidine (5 microM) to block sympathetic neurotransmission elicited frequency-dependent vasodilatation due to activation of sensory-motor nerves. Percentage relaxations were similar in preparations from pregnant and non-pregnant rats. 6. Dose-dependent endothelium-dependent vasodilatations to acetylcholine and ATP were similar in preparations from pregnant and non-pregnant rats. Endothelium-independent vasodilatation to sodium nitroprusside and to calcitonin gene-related peptide were also similar between the two groups. 7. There was no significant difference in the basal perfusion pressure of mesenteric arterial beds from control (21.3 +/- 1.0 mmHg, n = 24) and pregnant (20.2 +/- 1.2 mmHg, n = 23) rats. However, a step-wise increase in perfusate flow from 5 to 10, 15, 20 and 24ml min-1 produced smaller increases in perfusion pressure in pregnancy compared to the controls. L-NAME (100 microM) or indomethacin (10 microM) had no significant effect on the relationship between flow and perfusion pressure. 8. The present results show that prejunctional changes are involved in blunted sympathetic vasoconstriction of rat mesenteric arteries in pregnancy. Non-specific postjunctional changes are implicated in the reduced constrictor responses to applied methoxamine, vasopressin and endothelin, but not to ATP. In contrast, sensory-motor nerves and endothelium-dependent and -independent vasodilatation was unchanged. The decrease in receptor-mediated mesenteric arterial constrictor responsiveness in pregnancy does not appear to be due to acute modulation by NO or prostaglandins, but may involve changes in the distensibility of the bed and/or changes in wall thickness.
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PMID:Mesenteric arterial function in the rat in pregnancy: role of sympathetic and sensory-motor perivascular nerves, endothelium, smooth muscle, nitric oxide and prostaglandins. 873 Jul 40

Alveolar type II cells may be exposed to nitric oxide (.NO) from external sources, and these cells can also generate .NO. Therefore we studied the effects of altering .NO levels on various type II cell metabolic processes. Incubation of cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit this process. On the other hand, incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP content, and cellular oxygen consumption. The L-NAME effects are reversed by addition of L-arginine, the substrate for NOS. Production of .NO by type II cells is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than inducible NOS (iNOS), and is reduced in the absence of external calcium. Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content or on .NO production. These results indicate that alveolar type II cell lipid and energy metabolism can be affected by .NO and suggest that there may be cNOS activity in these cells.
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PMID:Nitric oxide alters metabolism in isolated alveolar type II cells. 876 Jan 28

1. The nature of neurotransmitter(s) involved in non-adrenergic non-cholinergic (NANC) relaxations induced by electrical stimulation (10 s trains, 1-8 Hz) was investigated in the precontracted longitudinal muscle-myenteric plexus preparation of the rat ileum. 2. Electrical stimulation of the tissue induced complex responses, consisting of a primary contraction, a primary relaxation, an off-relaxation and a rebound contraction, which were all tetrodotoxin(TTX)-sensitive. 3. Vasoactive intestinal polypeptide (VIP) and carbon monoxide (CO) did not induce relaxations. alpha-Chymotrypsin did not reduce the relaxations induced by electrical stimulation, while zinc protoporphyrin IX had non-specific effects. 4. Nitric oxide (NO) induced concentration-dependent relaxations. NG-nitro-L-arginine methylester (L-NAME) abolished the primary contractions and off-relaxations, while it partially reduced the primary relaxations. 5. ATP induced relaxations and ATP-desensitization of the tissues partially reduced the primary relaxations. Suramin and reactive blue 2 did not consistently influence the primary relaxations. 6. The ATP-induced relaxations were not influenced by L-NAME or TTX. The inhibitory effect of ATP-desensitization and L-NAME did not summate. 7. The cyclic AMP content of the tissue did not increase upon electrical stimulation or after addition of NO or ATP. The cyclic GMP content of the tissue increased upon electrical stimulation and addition of NO, but not after addition of ATP. 8. It is concluded that the relaxation induced by electrical stimulation consists of two types of responses. The off-relaxation is completely nitrergic, while the primary relaxation is mediated by NO, ATP and an as yet unknown transmitter which is not VIP or CO.
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PMID:ATP and nitric oxide: inhibitory NANC neurotransmitters in the longitudinal muscle-myenteric plexus preparation of the rat ileum. 876 96

1. Inhibitory junction potentials (IJPs) and relaxations evoked in response to field stimulation (supramaximal voltage, 0.1 ms, single stimulus and 5 stimuli at 5-40 Hz) of non-adrenergic non-cholinergic (NANC) nerves with atropine and phentolamine (each 1 microM) were measured in the guinea-pig internal anal sphincter (gpIAS). The mean resting membrane potential was -44.2 +/- 0.2 mV (n = 1119 cells from 260 preparations). 2. NANC nerve stimulation evoked frequency-dependent IJPs (19.7 +/- 1.1 mV, n = 165, 33 tissues to a single stimulus) and relaxations. IJPs consisted of two tetrodotoxin (1 microM)-sensitive components: one was abolished by apamin (0.3 microM) and the P2-purinoceptor antagonist suramin (100 microM); the other, smaller in amplitude, was sensitive to inhibitors of nitric oxide synthase (NOS, e.g. L-NAME, 100 microM) and the nitric oxide (NO) scavenger oxyhaemoglobin (HbO, 10 microM). 3. ATP (1 mM), vasoactive intestinal polypeptide (VIP, 0.01-0.25 microM) and pituitary adenylate cyclase-activating peptide (PACAP(1-27), 0.84 microM) each hyperpolarized and relaxed the gpIAS; only ATP responses resembled the evoked IJPs in time course. 4. The guanylyl cyclase inhibitor LY83583 (10 microM) abolished apamin-insensitive IJPs and relaxations. The cGMP phosphodiesterase inhibitor M&B 22948 (30 microM) and 8-Br-cGMP (100 microM) each hyperpolarized the gpIAS. 5. Two components comprise the IJP and relaxation evoked in response to NANC nerve stimulation in the gpIAS. One, sensitive to apamin, resembles the response to ATP and is modulated by purinoceptor antagonists; the other, apamin and suramin insensitive, is inhibited by NO antagonists.
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PMID:Neuronal mediators of inhibitory junction potentials and relaxation in the guinea-pig internal anal sphincter. 878 13

In view of the previously reported marked reduction in the number of neurons in the rat small intestine, the influence of age on the responses to electrical stimulation of the longitudinal muscle-myenteric plexus preparation of the ileum of young (3-4 months), adult (12-13 months) and old (24-25 months) rats was investigated. The differences in responses between the three age groups were varied. At the basal tone level, electrical train stimulation induced complex responses consisting of a primary contraction, which was partly cholinergic, a secondary contraction, which was completely cholinergic and a rebound contraction, which was partly cholinergic. These responses did not differ between young, adult and old rats. The inhibiting effects of atropine and potentiating effects of physostigmine on these responses did not change with age. The acetylcholine-induced concentration-response curve did not differ between the three age groups. Electrical train stimulation of the precontracted longitudinal muscle-myenteric plexus preparation under nonadrenergic noncholinergic (NANC) conditions induced multiphasic responses consisting of a primary contraction, a primary relaxation, a postrelaxation and a rebound contraction. The primary contraction and the postrelaxation, which were nitrergic in nature, were not influenced by age. The primary relaxation was slightly more pronounced in young rats. In young rats, this relaxation was partly inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and ATP desensitization, while in adult and old rats these primary relaxations were only influenced by ATP desensitization, but not by L-NAME. Nitric oxide-induced relaxations were similar in the three age groups. The cAMP content was not increased by electrical stimulation, while the cGMP content increased with electrical stimulation, but no differences due to age were observed. These results suggest that cholinergic responses in the rat small intestine are well-maintained with age while the nitrergic contribution to NANC relaxation decreases with age.
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PMID:Influence of age on cholinergic and inhibitory nonadrenergic noncholinergic responses in the rat ileum. 880 14

In isolated, constant-pressure perfused rat kidneys at basal vascular tone, injected P2 purinoceptor agonists evoked vasoconstriction (alpha, beta-methylene ATP > beta, gamma-methylene ATP > ATP-gamma-S > 2-methylthio ATP > ATP > ADP = UTP). In kidneys with raised tone, the nucleotides produced vasodilatation at low doses (2-methylthio ATP > ADP = ATP = ATP-gamma-S > UTP; alpha, beta-methylene ATP and beta, gamma-methylene ATP, inactive), and constriction at high doses (alpha, beta-methylene ATP > beta, gamma-methylene ATP > ATP-gamma-S > 2-methylthio ATP > ADP = ATP > UTP). Removal of the endothelium abolished the dilator responses to the agonists. NG-Nitro-L-arginine methylester (L-NAME, 5 x 10(-5) M) abolished vasorelaxation in response to 2-methylthio ATP, a response which could be restored by additional L-arginine (3 x 10(-3) M). Both vasodilatation and constriction due to the nucleotides remained unaffected by indomethacin (3 x 10(-6) M), S-(p-nitrobenzyl)-6-thioinosine (3 x 10(-5) M) and 8-phenyltheophylline (3 x 10(-6) M). Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 1-3 x 10(-6) M), inhibited vasoconstriction caused by alpha, beta-methylene ATP, 2-methylthio ATP and UTP, but not by ATP. Suramin (3 x 10(-5) M) caused a rightward shift of the dose-response curves for constriction caused by alpha, beta-methylene ATP (27-fold) and 2-methylthio ATP (5-fold), whereas the ATP curve was shifted to the left (20-fold). With Evans blue (10(-5) M), vasodilatation due to the nucleotides was abolished and the dose-response curves for vasoconstriction caused by ATP and UTP were shifted left more than 100-fold, the effect to both could not be antagonized by PPADS (3 x 10(-6) M). These results suggest: (1) the different rank orders of P2 purinoceptor agonist potencies for constrictor and dilator responses in perfused rat kidney are consistent with mediation via P2x and P2Y purinoceptors, respectively; (2) P2X purinoceptors, selectively sensitive to blockade by PPADS, are located on vascular smooth muscle; (3) endothelial P2Y purinoceptor stimulation results in vasodilatation involving NO synthesis but not release of prostanoids; (4) Evans blue, which appears to combine selective P2Y purinoceptor blockade and strong inhibition of ecto-nucleotidases, potentiates vasoconstriction in response to the degradable nucleotides, ATP, 2-methylthio ATP and UTP; (5) additionally, Evans blue unmasks a PPADS-insensitive P2U purinoceptor where the nearly equipotent nucleotides, ATP and UTP, can produce vasoconstriction.
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PMID:Characterization of vascular P2 purinoceptors in the rat isolated perfused kidney. 881 26

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