Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We investigated the role of nitric oxide (NO) and of vasoactive eicosanoids in the control of renal vascular resistance (RVR) and glomerular filtration rate (GFR) and of their responses to noradrenaline (NA). This study was conducted in single-pass perfused, isolated kidney preparations of the rat. 2. NA (63, 110 and 160 nM) dose-dependently increased RVR and to a lesser degree GFR. 3. In baseline conditions, N omega-nitro-L-arginine methylester (L-NAME, 100 microM) increased GFR more than RVR, thus demonstrating a basal release of NO which predominates in postglomerular vessels. 4. In kidneys stimulated with NA, L-NAME potentiated the increases in RVR but not in GFR. Indomethacin (1.5, 150 nM and 15 microM) did not alter GFR but markedly and dose-dependently reduced the NA-induced increase in RVR. Similar results were obtained with GR 32191B (10 and 100 microM), a prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor antagonist. 5. Indomethacin (15 microM) suppressed the enhancing effects of L-NAME on RVR responses to NA but did not affect those on GFR. 6. It is concluded that the mechanisms of the response to NA differ among pre- and postglomerular vessels. In preglomerular vessels the vasoconstrictor action and the NO release depend upon the activation of PGH2/TxA2 receptors, while both are eicosanoid-independent in the postglomerular vessels.
Br J Pharmacol 1993 Sep
PMID:Eicosanoid-dependence of responses of pre- but not postglomerular vessels to noradrenaline in rat isolated kidneys. 822 Aug 83

1. Calcitonin gene-related peptide (CGRP) potently enhances mucosal blood flow in the rat stomach. The aim of this study was to examine whether CGRP also dilates extramural arteries supplying the stomach and whether the vasodilator action of CGRP involves nitric oxide (NO). 2. Rat CGRP-alpha (0.03-1 nmol kg-1, i.v.) produced a dose-dependent increase in blood flow through the left gastric artery (LGA) as determined by an ultrasonic transit time technique in urethane-anaesthetized rats. Blockade of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 20 and 60 mumol kg-1, i.v.) significantly reduced basal blood flow (BF) in the LGA and attenuated the hyperaemic activity of CGRP by a factor of 2.8-4. D-NAME tended to enhance basal BF in the LGA but had no influence on the dilator activity of CGRP. The ability of vasoactive intestinal polypeptide to increase left gastric arterial blood flow remained unaltered by L-NAME. 3. L-NAME (20 and 60 mumol kg-1, i.v.) evoked a prompt and sustained rise of mean arterial blood pressure (MAP) and caused a slight decrease in the hypotensive activity of CGRP. In contrast, D-NAME induced a delayed and moderate increase in MAP and did not influence the hypotensive activity of CGRP. 4. Rat CGRP-alpha dilated the isolated perfused bed of the rat LGA precontracted with methoxamine and was 3 times more potent in this respect than rat CGRP-beta. The dilator action of rat CGRP-alpha in this preparation was not affected by L-NAME or D-NAME (40 microM). 5. L-NAME (60 micromol kg-1, i.v.) reduced gastric mucosal blood flow as assessed by laser Doppler flowmetry and diminished the hyperaemic activity of rat CGRP-alpha in the gastric mucosa by a factor of 4.5, whereas D-NAME was without effect.6. These data show that CGRP is a potent dilator of mucosal and extramural resistance vessels in the rat stomach. Its dilator action involves both NO-dependent and NO-independent mechanisms.
Br J Pharmacol 1993 Sep
PMID:Nitric oxide-dependent and -independent hyperaemia due to calcitonin gene-related peptide in the rat stomach. 822 Sep 1

1. The role of nitric oxide in the cerebral circulation under basal conditions and after vasodilator stimulation was studied in instrumented, conscious goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 6 unanaesthetized goats, blood flow to one brain hemisphere (electromagnetically measured), systemic arterial blood pressure and heart rate were continuously recorded. L-NAME (35 mg kg-1 by i.v. bolus) decreased resting cerebral blood flow by 43 +/- 3%, increased mean arterial pressure by 21 +/- 2%, and decreased heart rate by 41 +/- 2%; cerebrovascular resistance increased by 114 +/- 13% (P < 0.01); the immediate addition of i.v. infusion of L-NAME (0.15-0.20 mg kg-1 during 60-80 min) did not significantly modify these effects. Cerebral blood flow recovered at 72 h, arterial pressure and cerebrovascular resistance at 48 h, and heart rate at 6 days after L-NAME treatment. 3. A second treatment with L-NAME scheduled as above reproduced the immediate haemodynamic effects of the first treatment, which (except bradycardia) reversed with L-arginine (200-300 mg kg-1 by i.v. bolus). 4. Acetylcholine (0.01-0.3 micrograms), sodium nitroprusside (3-100 micrograms) and diazoxide (0.3-9 mg), injected into the cerebral circulation of 5 conscious goats, produced dose-dependent increases in cerebral blood flow, and decreases in cerebrovascular resistance; sodium nitroprusside (30 and 100 micrograms) also caused hypotension and tachycardia. 5. The reduction in cerebrovascular resistance from resting levels (in absolute values) to lower doses,but not to the highest dose, of acetylcholine was diminished, to sodium nitroprusside was increased, and to diazoxide was unaffected after L-NAME, compared to control conditions. The effects on cerebrovascular resistance to acetycholine normalized within 24 h and to sodium nitroprusside within 48 h after L-NAME treatment.6. This study provides information about the evolution of the changes in cerebral blood flow and cerebrovascular reactivity after inhibition of endogenous nitric oxide in conscious animals. The results suggest: (a) endogenous nitric oxide is involved in regulation of the cerebral circulation by producing a resting vasodilator tone, (b) the cerebral vasodilatation to acetylcholine is mediated, at least in part, by nitric oxide release, and (c) inhibition of nitric oxide production induces supersensitivity of cerebral vasculature to nitrovasodilators.
Br J Pharmacol 1993 Sep
PMID:Cerebral blood flow and cerebrovascular reactivity after inhibition of nitric oxide synthesis in conscious goats. 822 Sep 4

In the perfused rat mesentery, when adrenergic nerves were blocked with guanethidine and vascular smooth muscle tone was increased with methoxamine, transmural field stimulation caused a dilator response. Bradykinin significantly suppressed vasodilator responses to a transmural field stimulation in a concentration-dependent manner. After pretreatment with saponin to damage endothelial cells, bradykinin still suppressed vasodilator responses to transmural field stimulation. The effect of bradykinin was unaltered by indomethacin. N omega-Nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, abolished the inhibition of vasodilator responses to transmural field stimulation elicited by bradykinin. However, in the presence of L-arginine and L-NAME the inhibitory effect of bradykinin reappeared. Furthermore, methylene blue itself caused potentiation of vasodilator responses to transmural field stimulation and reversed the effect of bradykinin. These findings suggest that bradykinin can produce an inhibitory modulation of the actions of sensory nerves in the perfused rat mesentery and that the effect of bradykinin may be mediated by nitric oxide released from non-adrenergic, non-cholinergic nerves.
Eur J Pharmacol 1993 Sep 07
PMID:The regulatory effect of bradykinin on the actions of sensory nerves in the perfused rat mesentery is mediated by nitric oxide. 822 22

To assess the possible role of spinal nitric oxide (NO) synthesis in nociceptive processing, we examined the effect of intrathecal (i.t.) injection of arginine analogs that act as alternate substrates for NO synthase and thus inhibit NO production. NG-nitro-L-arginine ester (r-NAME) and NG-monomethyl-L-arginine (L-NMMA) produced a dose-dependent, stereospecific inhibition of the second phase (10-60 min; ED50, 135 and 246 nmol) of the formalin test with minimal effect on the first phase (0-9 min; ED50 > 1.1 mumol). The inhibitory action of L-NAME was dose-dependently reversed by i.t. L-arginine (ID50, 4.9 mumol) but not by D-arginine (ID50 > 14 mumol). The suppression of the second-phase formalin response by L-NAME was similar whether administered before or after formalin injection into the rat paw. Spinal administration of L-NAME (370 nmol), but not D-NAME (3.7 mumol), also blocked thermal hyperalgesia induced by i.t. injection of N-methyl-D-aspartate (NMDA; 6.8 nmol). The effect of L-NAME was reversed by L-arginine (4.7 mumol) but not with D-arginine (14 mumol). None of the compounds, L-NAME, D-NAME or L-arginine, when injected alone, had any effect on normal thermal response latencies or on the 52.5 degrees C hot plate. These studies indicate that modulation of spinal NO synthesis can diminish the facilitated processing of afferent activity which is induced by a continued afferent barrage (second phase of the formalin test). This hyperalgesic component appears initiated by the activation of a spinal NMDA receptor that, through the generation of NO, leads to the observed augmented processing of afferent input and the associated hyperalgesic component of the subsequent pain behavior.
Pain 1993 Sep
PMID:Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats. 823 43

1. In order to investigate the control of renal vascular tone by endothelin (ET) and endothelium-derived relaxing factor (EDRF) under basal conditions, we infused intravenously anti-ET-1/3 antibodies (a-ET-1/3) and NG-nitro-L-arginine methyl ester (L-NAME) in split hydronephrotic rat kidneys. 2. A 25 min I.V. infusion of a-ET-1/3 (4.0 x 10(-13) mol kg-1 min-1) induced a time-dependent vasodilatation of arcuate (16.5%) and interlobular arteries (18.6%) as well as an increase of glomerular blood flow (GBF) by 32%. 3. Inhibition of EDRF synthesis by L-NAME produced a marked vasoconstriction of arcuate arteries (17.1%) and efferent (20.1%) arterioles and a decrease of GBF by 43%. 4. Co-infusion of a-ET-1/3 and L-NAME induced efferent vasoconstriction by 19.5%, whereas preglomerular vessel diameters remained unchanged. 5. The specificity of a-ET-1/3 effects was confirmed by simultaneous I.V. application of a-ET-1/3 and ET-1 (160 ng I.V.) which produced no significant vascular effects. Injection of ET-1 alone constricted arcuate arteries and decreased glomerular blood flow by 25%. 6. Experiments in normal rat kidneys with a-ET-1/3 I.V. revealed an increase of renal blood flow by 21%. 7. Our results demonstrate a physiological control of basal vascular tone in larger preglomerular arterioles by ET and EDRF. Efferent arteriolar tone is predominantly controlled by EDRF.
J Physiol 1993 Sep
PMID:Endothelin and endothelium-derived relaxing factor control of basal renovascular tone in hydronephrotic rat kidneys. 827 Dec 16

Wistar rats given a nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME), for 4 weeks develop time- and dose-dependent hypertension without cardiac hypertrophy. This initial study of the relation between left ventricular weight and L-NAME-induced hypertension has now been extended by giving 50 mg/kg per day L-NAME to Wistar rats (n = 30) for 8 weeks and comparing results with those from control rats (n = 10) and two-kidney, one clip rats (n = 14). Although L-NAME rats and two-kidney, one clip rats had increased systolic blood pressures during the last 3 weeks of the experiment (202 +/- 24 and 224 +/- 16 mm Hg, respectively), the ratio of left ventricular weight to body weight of L-NAME rats (2.12 +/- 0.32 mg/g) was not statistically different from that of control rats (1.93 +/- 0.13 mg/g), whereas that of two-kidney, one clip rats was increased (2.85 +/- 0.20 mg/g). The plasma renin activity of L-NAME rats was not significantly different from that of control rats. Two L-NAME rat subgroups were defined according to the presence of left ventricular hypertrophy (ratio of left ventricular weight to body weight > 2.19 mg/g, control mean +2 SD) (6 of 25) or its absence (19 of 25). Systolic blood pressure, plasma renin activity, and cardiac angiotensin converting enzyme activity of L-NAME rats with left ventricular hypertrophy were significantly higher than those of the subgroup without.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Sep
PMID:Cardiac weight in hypertension induced by nitric oxide synthase blockade. 834 31

This study investigates the effects of inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME), the inhibition of prostaglandin synthesis with indomethacin and the combined effects on gastric mucosal hyperemia of ketamine-anesthetized rats with portal hypertension induced by partial portal vein ligation. The hydrogen gas-clearance technique was used for measurement of gastric mucosal blood flow. Blood pressure increased with L-NAME administration in a similar manner in portal-hypertensive and sham-operated rats. Low doses of L-NAME (1 and 3 mg/kg, intravenously) caused a significant and dose-dependent reduction in gastric mucosal blood flow in portal-hypertensive rats but had no effect on sham-operated animals. With a higher dose of L-NAME (13 mg/kg, intravenously), a significant decrease in gastric mucosal blood flow was observed in both portal-hypertensive and sham-operated rats. Indomethacin pretreatment (5 mg/kg, subcutaneously) caused a significant decrease in basal gastric mucosal blood flow of portal-hypertensive rats but did not modify this parameter in sham-operated animals. In sham-operated rats pretreated with indomethacin, the lower dose of L-NAME (3 mg/kg) did not significantly modify basal gastric mucosal blood flow. Likewise, pretreatment with indomethacin in sham-operated rats did not augment the significant reduction in gastric mucosal blood flow produced by the higher dose of L-NAME. In portal-hypertensive rats the significant dose-dependent reduction in gastric mucosal blood flow induced by L-NAME (3 and 13 mg/kg) was not significantly altered by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatology 1993 Sep
PMID:Involvement of nitric oxide and prostaglandins in gastric mucosal hyperemia of portal-hypertensive anesthetized rats. 835 4

The administration by aerosol of the nitric oxide (NO) synthesis inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) or Ng-monomethyl-L-arginine (L-NMMA), to spontaneously breathing anesthetized guinea pigs resulted in a significant enhancement of lung resistance (RL) after increasing intravenous doses of histamine. The maximal response was increased (p < 0.01) by 126% (L-NAME) and 282% (L-NMMA) compared with the control groups. This effect was inhibited by giving an aerosol of the NO precursor L-arginine (L-Arg) but not by its inactive enantiomer D-arginine (D-Arg). Perfusion through the lumen of guinea pig tracheal tubes in vitro with nitric oxide synthesis inhibitors (120 microM) resulted in a significant increase in basal tone, suggesting a role for NO in the maintenance of basal tone. In addition, the histamine concentration-response curve was significantly shifted upward: the maximal response was increased (p < 0.01) by 335% (L-NAME) and 250% (L-NMMA) compared with the control group. This effect was concentration dependently inhibited by coincubation with L-Arg (120, 200, and 400 microM), but not with D-Arg (200 microM). Furthermore, removal of the epithelium resulted in an upward shift in the histamine concentration-response curve: the maximal response was increased by 185%. However, incubation with L-NAME did not further increase tracheal responsiveness to histamine, but addition of L-Arg (360 microM), when a plateau was reached, relaxed the tissues to control values. Nitric oxide synthesis inhibition did not change the responsiveness of intact tissues in vitro after intraluminal stimulation with leukotriene D4, serotonin, or the cholinergic agonist arecoline.(ABSTRACT TRUNCATED AT 250 WORDS)
Am Rev Respir Dis 1993 Sep
PMID:Nitric oxide synthesis inhibitors induce airway hyperresponsiveness in the guinea pig in vivo and in vitro. Role of the epithelium. 836 46

Endothelium-dependent relaxation is associated with smooth muscle hyperpolarization in many arteries which may account for relaxation that persists in the presence of nitric oxide inhibitors such as NG-nitro-L-arginine methyl ester (L-NAME). Acetylcholine (ACh)-induced relaxations of the rabbit thoracic and abdominal aorta and iliac and carotid arteries were studied for the relative contribution of nitric oxide-dependent and -independent mechanisms in rings suspended for measurement of isometric tension. Although relaxation of the thoracic aorta to ACh (10(-6) M) was almost blocked completely by L-NAME (3 x 10(-5) M), the maximal relaxation in the abdominal aorta, carotid and iliac arteries was only reduced by 28, 26 and 62%, respectively. In rings of abdominal aorta, L-NAME blocked the ACh-stimulated (10(-6) M) rise in cyclic GMP verifying that relaxation which persists in L-NAME-treated rings is not mediated by nitric oxide. The L-NAME resistant response was nearly abolished by elevated external K+ in rings of abdominal aorta and carotid artery, suggesting this relaxation may be mediated by a membrane potential sensitive mechanism. Furthermore, tetraethylammonium (10(-3) M) partially and charybdotoxin (5 x 10(-8) M) completely inhibited the remaining L-NAME-resistant relaxation in both abdominal aorta and carotid artery, suggesting a role for Ca(++)-activated K(+)-channels. Blockers of ATP-sensitive K+ channels also inhibited the L-NAME resistant relaxation in the abdominal aorta only.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1993 Sep
PMID:Potassium channel-mediated relaxation to acetylcholine in rabbit arteries. 839 36


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