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

The extrinsic neural pathways and transmitter mechanisms involved in neural influences controlling lower oesophageal sphincter (LOS) pressure have been evaluated in three groups of experiments in urethane anaesthetized rats. A miniature perfused sleeve/sidehole catheter measured gastric, LOS and oesophageal pressures. Group 1: Vago-vagal and vago-spinal reflex pathways were activated simultaneously via the central nervous system by stimulation of the central cut end of the left vagus. This caused a prolonged drop in LOS pressure with a rapid onset and a slow return to baseline. Subsequent right (bilateral) vagotomy in these animals increased basal LOSP (P < 0.001). Central vagal stimulation-induced reduction of LOSP was not significantly changed in amplitude but was shorter in duration (P < 0.01) than before bilateral vagotomy. IV administration of the 5-HT3 receptor antagonist granisetron (50 micrograms/kg), after bilateral vagotomy had no effect on the response to central vagal stimulation. The nitric oxide (NO) synthase inhibitor L-nitroarginine methyl ester (L-NAME) (100 mg/kg) reduced the depth of relaxation (P < 0.01) and temporarily increased basal LOSP. Propranolol (1.5 mg/kg, i.v.) subsequently increased basal LOSP (P < 0.01), but had no further effect on the vagal stimulation-induced reduction in LOSP. Alpha adrenergic blockade with phentolamine (1 mg/kg, i.v.) decreased basal LOSP (P < 0.01), and nearly abolished the response to vagal stimulation (P < 0.01). Group 2: Both alpha 1- and alpha 2-adrenoceptors were shown to be involved by the combined use of the more selective antagonists yohimbine (1 mg/kg, i.v.) and prazosin (200 micrograms/kg) in place of phentolamine. Group 3: To observe neurotransmitter mechanisms in the vago-vagal pathway, central left vagal stimulation was performed after left vagotomy, and subsequently after blockade of sympathetic motor pathways with guanethidine (5 mg/kg), leaving intact efferent pathways in the right vagus. Guanethidine increased basal LOSP (P < 0.01), and reduced the duration of vagal-induced LOS relaxation (P < 0.05). Depth of relaxation was unchanged. Subsequently, granisetron and L-NAME had no significant effects. Finally, additional right vagotomy abolished the remaining response. Our data indicate the existence of vago-spinal and vago-vagal inhibitory reflex pathways to the rat LOS. The inhibitory vago-spinal pathway is mainly alpha-adrenergic, and has a minor NO-mediated component, but no 5-HT3 receptor-mediated mechanism. In the vago-vagal pathway, no significant involvement of NO-mediated or 5-HT3 receptor-mediated effects was observed. Other non-adrenergic inhibitory mechanisms were, however, apparent.(ABSTRACT TRUNCATED AT 400 WORDS)
J Auton Nerv Syst 1994 Sep
PMID:Transmitter mechanisms in vagal afferent-induced reduction of lower oesophageal sphincter (LOS) pressure in the rat. 796 67

Isolated equine digital veins were examined in vitro to study the importance of the endothelium in the responses to both vasodilator and vasoconstrictor agents and to characterise the endothelial-derived mediators involved. Carbachol (Cch; 1 microM) and bradykinin (Bk; 1 nM) caused relaxation of U44069-induced tone by 79.5 +/- 0.35% and 73.7 +/- 4.0% respectively. Mechanical removal of the endothelium completely prevented relaxant responses to Cch and to Bk showing they were mediated by the endothelium. Treatment of veins with NG-nitro-L-arginine methyl ester (L-NAME; 30 and 300 microM) inhibited vasorelaxant responses to both Cch and Bk whereas the cyclooxygenase inhibitor, ibuprofen (10 microM) had no inhibitory effect. The inhibitory action of L-NAME on the relaxations produced by Cch was partly reversed by L-arginine (3 and 10 mM). Cch-relaxations were potentiated in the presence of super oxide dismutase (15 units/ml) and inhibited by methylene blue (10 microM). The vasorelaxant effects of ATP (0.01 microM to 0.1 mM) were not dependent on the presence of the endothelium and the selective P2y receptor agonist, 2-methylthio-ATP proved to be ineffective as a vasodilator. Removal of the endothelium did not enhance the vasoconstrictor effects of the alpha 1 adrenoceptor agonist phenylephrine (0.01 microM to 0.1 mM) and treatment with L-NAME (300 microM) did not change the vasoconstrictor responses to 5-HT (1 nM to 10 microM) or the alpha 2 adrenoceptor agonist BHT-920 (1 nM to 1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Equine Vet J 1994 Sep
PMID:The role of nitric oxide in the responses of equine digital veins to vasodilator and vasoconstrictor agents. 798 41

Nitric oxide (NO) synthesized from L-arginine is an endogenous vasodilator and inhibitor of platelet adhesion and aggregation. Gram-negative lipopolysaccharide (LPS) can induce NO synthesis, which may mediate the pathophysiologic effects of endotoxemia. In addition, our previous studies suggested that LPS-induced NO may protect against thrombosis in rats. In the present study, male Sprague-Dawley rats given LPS (0.1 mg/kg) i.p. increased their urinary excretion of NO2 + NO3 (stable end-products of NO) by 4.3-fold. Rats given 10 micrograms/kg/hr i.v. of nitroglycerin (GTN), an exogenous NO donor, showed a similar increase. L-NAME, an inhibitor of NO synthesis, abrogated the increase in urinary NO2 + NO3 in LPS-treated rats but not in rats given GTN. Glomerular thrombosis developed in rats given LPS + L-NAME (thrombosis score = 3.02 +/- 0.4), while those given LPS + L-NAME + GTN were largely protected (thrombosis score = 1.37 +/- 0.5, P < 0.05). Atrial natriuretic peptide (ANP), an NO-independent vasodilator, neither increased urinary NO2 + NO3 nor prevented glomerular thrombosis (thrombosis score = 2.68 +/- 0.5, NS). Hydralazine, another vasodilator without effects on NO or platelets, also failed to prevent glomerular thrombosis in rats given LPS + L-NAME. We conclude that in endotoxemia, the antithrombogenic properties of endogenously synthesized NO are important in preventing alomerular thrombosis. The exogenously NO donor, GTN, can substitute for the antithrombogenic effect of endogenous NO. Clinically, administration of NO synthesis inhibitors to treat endotoxic shock may need to be combined with concomitant administration of exogenous NO donors to prevent microvascular thrombosis.
Kidney Int 1994 Sep
PMID:Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. 799 92

In heartworm-infected dogs, circulating filarial factors appear to be responsible for the seasonal depression of endothelium-dependent responses seen in the in vivo femoral artery. The effect of heartworm infection on vascular responses of the femoral artery in vitro, when the vessel is not constantly exposed to circulating factors, is unknown. Experiments were designed to test the hypothesis that in vivo exposure to circulating filarial factors leads to changes in the magnitude and mechanism of endothelium-dependent relaxation that are demonstrable in vitro. Rings of femoral artery from heartworm-infected and noninfected control dogs were suspended in muscle baths, and dose-response relationships to endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilators were done. To determine the mechanism of relaxation, dose-response relationships were also done in the presence of an inhibitor of nitric oxide synthase (L-NAME), an inhibitor of guanylate cyclase (methylene blue), or an inhibitor of cyclooxygenase (mefenamic acid). Heartworm infection did not depress endothelium-dependent relaxation of the femoral artery in vitro. Furthermore, the mechanism of relaxation in heartworm and control femoral artery is identical. These data suggest that the effect of circulating filarial factors that alter the magnitude and mechanism of relaxation in systemic vessels in heartworm-infected dogs rapidly disappears in their absence. This results has important bearing on the dynamics of heartworm-induced pathophysiological changes during infection and could influence the nature and chronology of responses to therapy.
Exp Parasitol 1994 Sep
PMID:Dirofilaria immitis: depression of endothelium-dependent relaxation of canine femoral artery seen in vivo does not persist in vitro. 805 79

Two lines of mice were produced by bidirectional selective breeding: one resistant (CAR-R) and one susceptible (CAR-S) to two-stage skin carcinogenesis by dimethylbenz(a)anthracene and 12-O-tetradecanoyl-phorbol-13-acetate. The dimethylbenz(a)anthracene-DNA adduct formation was compared in the two lines by a postlabeling procedure so as to determine whether the striking interline difference observed as to tumor incidence could (in part) be due to differences in the formation of DNA-reactive metabolites. Results show that qualitatively, adduct profiles in CAR-R and CAR-S epidermis are similar. Quantitatively, the total binding level is slightly higher in CAR-S versus CAR-R mice during the 30-day follow-up. However, these minor differences do not increase in function of the response to selection observed through three consecutive generations. A 2- or 4-week promotion with 12-O-tetradecanoylphorbol-13-acetate enhances the decrease of adduct level in the two lines. This effect is somewhat more pronounced in CAR-S mice. Results strongly suggest that the expression of the genes responsible for CAR-R/CAR-S phenotypic difference affects mainly the postinitiation stages.
Cancer Res 1994 Sep 01
PMID:Comparison of 7,12-dimethylbenz(a)anthracene-DNA adduction in the epidermis of two lines of mice selected for resistance (CAR-R) or susceptibility (CAR-S) to skin carcinogenesis. 806 56

We examined the hypothesis that the coronary vasomotor responses to etomidate (ETO), propofol (PRO), and sodium thiopental (STP) are mediated through contrasting effects on the resting nitric oxide (NO)-dependent vasodilator tone that opposes adrenergic vasoconstrictor activity in the intact dog. Circumflex flow (CxF) responses to randomized intracoronary microinjections (0.3 mL) of normal saline (NS), alkalinized saline (AS), intralipid (IL), adenosine (ADE, 17 micrograms), acetylcholine (ACh, 1.25 micrograms), ETO (6, 12, 60 micrograms), PRO (30, 60, 300 micrograms), and STP (75, 150, 750 micrograms) were quantified in eight isoflurane-anesthetized dogs with fixed ventricular rates (100 bpm). Injections were repeated during intravenous (IV) infusion (50 mg/kg + 1 mg.kg-1.min-1) of NG-nitro-L-arginine methyl ester (L-NAME). ADE and ACh transiently increased CxF to 305% +/- 20% (P < 0.001) and 310% +/- 29% (P < 0.001) of resting values, respectively. ETO had no effect, whereas PRO (300 micrograms) provoked small transient increases in CxF to 135% +/- 4% (P < 0.05) of control. Responses to STP (750 micrograms) were characterized by momentary decreases to 74% +/- 4% (P < 0.001), followed immediately by increases to 183% +/- 11% (P < 0.001) of resting values; NS AS, and IL had no effect. The momentary decreases with STP (750 micrograms) were significantly augmented during NO inhibition with CxF declining to 49% +/- 7% (P < 0.001) of resting values, whereas the secondary increase was unchanged. With L-NAME, CxF responses to ACh were attenuated to 32% +/- 3% (P < 0.001) of control, whereas responses to ADE, ETO, and PRO were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesth Analg 1994 Sep
PMID:Comparative effects of nitric oxide inhibition on the coronary vasomotor responses to etomidate, propofol, and thiopental in anesthetized dogs. 806 46

Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < 0.001) associated with selective necrosis of 49 +/- 9% of medullary thick ascending limbs. Hemodynamic studies using laser-Doppler probes revealed that when injected alone, iothalamate increased outer medullary blood flow to 196 +/- 25% of baseline (P < 0.001). Pretreatment by L-NAME or indomethacin both reduced basal medullary blood flow and transformed the medullary vasodilator response to radiocontrast into vasoconstriction, with a prolonged reduction of medullary blood flow to less then half of baseline. Combined administration of indomethacin, L-NAME, and iothalamate lowered medullary blood flow to 12 +/- 4% of baseline. We conclude that prostanoids and nitric oxide have an important protective role in the renal response to radiocontrast material. Reduced synthesis of these vasoactive substances in renal/vascular diseases may predispose patients to radiocontrast nephropathy.
J Clin Invest 1994 Sep
PMID:Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. 808 47

Recently, in vivo and in vitro studies have implicated nitric oxide as a mediator of the vascular effects of angiotensin-converting enzyme inhibitors (ACEIs). In the present study we hypothesized that N-acetyl-L-cysteine (NAC), by increasing the availability of reduced sulfhydryl groups, would enhance the antihypertensive response to the ACEIs captopril and enalaprilat by a mechanism dependent on nitric oxide. The experiments were performed on instrumented, indomethacin-pretreated, awake spontaneously hypertensive rats (SHRs). Thirty minutes after a bolus of captopril (10 mg/kg iv) was administered, blood pressure decreased from 167 +/- 5 to 147 +/- 6 mmHg (n = 8). The pretreatment with the donor of thiol groups NAC (300 mg/kg iv) potentiated the depressor response to captopril because blood pressure decreased from 172 +/- 3 to 139 +/- 4 mmHg (n = 6). At the dose of 60 micrograms/kg iv, the ACEI enalaprilat did not acutely modify the blood pressure of SHRs (from 172 +/- 5 to 167 +/- 4 mmHg; n = 6). However, when the SHRs were pretreated with NAC, the same dose of enalaprilat significantly reduced blood pressure from 176 +/- 5 to 151 +/- 5 mmHg (n = 6). This potentiation of the depressor response to ACEIs, due to NAC, was not observed when SHRs were pretreated with the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 50 micrograms.kg-1.min-1 iv). The results of this study suggest that NAC, a donor of sulfhydryl groups, potentiates the antihypertensive response to captopril and enalaprilat in SHR by a nitric oxide-dependent mechanism.
Am J Physiol 1994 Sep
PMID:N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. 809 21

The aim of this study was to assess regional haemodynamic changes in conscious Brattleboro rats during chronic ingestion of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Animals were instrumented with renal, mesenteric and hindquarters pulsed Doppler flow probes and an intra-arterial catheter, and haemodynamic measurements were made before, during and after 14 days' exposure to L-NAME (0.01 mg ml-1 in the drinking water). Within 6 h after addition of L-NAME to the drinking water, mean arterial blood pressure was increased (maximum, 33 +/- 6 mm Hg), and remained so until L-NAME was withdrawn, whereupon blood pressure returned to normal levels within 24 h. The hypertension was accompanied by a transient reduction in mesenteric blood flow, and a more persistent reduction in hindquarters blood flow. Mesenteric and, particularly, hindquarters vascular conductance showed a sustained reduction. However, during ingestion of L-NAME, renal blood flow was not diminished and, over the final 4 days of exposure to L-NAME there was no significant renal vasoconstriction. All regional haemodynamic effects of L-NAME were lost within 24 h of its withdrawal. Hence, as with shorter periods of exposure to the less potent NO synthase inhibitor, NG-monomethyl-L-arginine, the hypertension caused by L-NAME is dependent on its continued administration, and is associated with a particularly marked hindquarters vasoconstriction.
Blood Press 1993 Sep
PMID:Regional haemodynamics in Brattleboro rats during chronic ingestion of NG-nitro-L-arginine methyl ester. 820 18

The influence of epithelium removal on the effects of contractile substances on airway responsiveness was investigated on the guinea-pig perfused bronchioles. A gentle rubbing of the luminal surface with a pipe cleaner significantly shifted to the left the concentration-response curves evoked by histamine (3 x 10(-12)-10(-4) M) and acetylcholine (10(-9)-10(-3) M) and decreased the relaxation response to fenoterol (10(-12)-2 x 10(-5) M). In contrast, removal of epithelium did not alter the responses to K+ (4.7 x 10(-3)-1.2 x 10(-1) M), theophylline (10(-8)-10(-2) M), sodium nitroprusside (4 x 10(-10)-4 x 10(-5) M) or papaverine (10(-4) M). In intact preparations treated with indomethacin (10(-5) M), histamine and acetylcholine induced contractions similar to that produced by rubbed tissues whereas relaxation induced by fenoterol was not modified. 10(-5) M tranylcypromine (inhibitor of prostacyclin synthesis) or 10(-6) M L-NAME (NG Nitro-L-Arginine Methyl Ester, a nitric oxide synthesis inhibitor) did not alter any concentration-response curves. Whereas prostaglandin E2 had no effect, prostaglandin E1 (10(-12)-10(-5) M) induced concentration-dependent relaxation, indicating that this prostanoid could be an epithelium-derived relaxing factor. These results suggest that epithelium of small caliber airways could release a cyclooxygenase product, namely a prostanoid, involved in the epithelium-dependent modulation in response to contractile drugs.
Pulm Pharmacol 1993 Sep
PMID:Do perfused small caliber airways of guinea-pig release an epithelium-dependent relaxing factor? 821 76


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