Inhibition of Acetylcholinesterase Selectively Potentiates NG-Monomethyl-l-Arginine-Resistant Actions of Acetylcholine in Human Forearm Vasculature

1995 ◽  
Vol 88 (1) ◽  
pp. 111-117 ◽  
Author(s):  
P. J. Chowienczyk ◽  
J. R. Cockcroft ◽  
J. M. Ritter
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Brachial Artery ◽  
Acetylcholinesterase Inhibitor ◽  
Sensory Nerve ◽  
High Dose ◽  
Nitric Oxide Synthase Inhibitor ◽  
Blood Flows ◽  
Human Forearm ◽  
Synthase Inhibitor

1. NG-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase inhibitor) inhibits vasodilator responses to acetylcholine but not methacholine in human forearm vasculature. To investigate whether this difference results from the relative susceptibility of these agonists to hydrolysis by acetylcholinesterase, we studied vasodilator responses to brachial artery administration of acetylcholine alone and in the presence of the acetylcholinesterase inhibitor edrophonium. 2. Vasodilator responses to constant-rate brachial artery infusions of acetylcholine were biphasic, with an initial peak response fading over 2 min to a plateau. Fade [(peak—plateau)/peak × 100%] was dose dependent (P < 0.02), ranging from 43 ± 7% (mean ± SEM) at low dose (16 nmol/min) to 9 ± 8% at high dose (83 nmol/min). 3. Edrophonium (0.5 μmol/min intra-arterially) alone produced no change in forearm blood flow but increased blood flow responses to acetylcholine (P < 0.01), causing an approximately 10-fold reduction in the dose required to increase plateau blood flow by 10 ml min−1 100 ml−1. 4. Responses to low doses of acetylcholine alone (16 and 41 nmol/min) faded more (P < 0.01) than those to doses of acetylcholine with edrophonium chosen to produce similar plateau blood flows. Responses to acetylcholine (41 nmol/min) also faded more (P < 0.01) than those to methacholine (5 nmol/min), producing matched plateau flows. 5. Peak and plateau responses to acetylcholine (41 nmol/min) were reduced (P < 0.01) by similar amounts (47 ± 15% and 37 ± 13% respectively, P = 0.39) by coinfusion of l-NMMA (4 μmol/min). l-NMMA inhibited responses to acetylcholine more than matched responses to acetylcholine with edrophonium (P < 0.01). 6. These results suggest that the actions of acetylcholine in human forearm resistance vessels are mediated both through an l-NMMA-sensitive pathway (l-arginine/nitric oxide pathway) that exhibits biphasic characteristics and through an l-NMMA-resistant pathway. The l-NMMA-resistant pathway is selectively potentiated by edrophonium. Inhibition of acetylcholinesterase by edrophonium may increase concentrations of acetylcholine deep to the endothelium and favour NO-independent actions on smooth muscle or sensory nerve endings mediating vasodilatation.

Sex differences and role of nitric oxide in blood flow of canine urinary bladder

1999 ◽  
Vol 276 (2) ◽  
pp. R407-R413 ◽  
Author(s):  
Michel A. Pontari ◽  
Michael R. Ruggieri
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Intravesical Pressure ◽  
Bladder Mucosa ◽  
Arterial Infusion ◽  
Nitric Oxide Synthase Inhibitor ◽  
Doppler Flowmetry ◽  
Muscle Perfusion ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor

Continuous measurements were made of bladder blood flow by laser Doppler flowmetry in anesthetized dogs during bladder filling and emptying. In both mucosa and muscle, perfusion was inversely proportional to intravesical pressure. There was significantly greater perfusion in the bladder mucosa of males than females at baseline and up to 10 cm water filling pressure but not in the muscle. Intra-arterial infusion of the nitric oxide synthase inhibitor N G-nitro-l-arginine produced a significant decrease in resting bladder perfusion in the mucosa only, with no differences seen in the response to intravesical pressure. Intra-arterial infusion ofl-arginine produced a significant increase in the level of perfusion in the mucosa seen immediately after the bladder was drained. No changes were observed in muscle perfusion afterl-arginine. These results suggest that the perfusion of the bladder mucosa differs by gender and is regulated differently than the bladder muscle, possibly related to the different function of the two layers.

Nitric Oxide Modulation of Pulmonary Blood Flow Distribution in Lobar Hypoxia 

1995 ◽  
Vol 82 (5) ◽  
pp. 1216-1225 ◽  
Author(s):  
Filip Freden ◽  
Shao Z. Wei ◽  
Jan E. Berglund ◽  
Claes Frostell ◽  
Goran Hedenstierna
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Lower Lobe ◽  
Nitric Oxide Production ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endogenous Nitric Oxide ◽  
Nitric Oxide Inhalation ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Background Nitric oxide, endogenously produced or inhaled, has been shown to play an important role in the regulation of pulmonary blood flow. The inhalation of nitric oxide reduces pulmonary arterial pressure in humans, and the blockade of endogenous nitric oxide production increases the pulmonary vascular response to hypoxia. This study was performed to investigate the hypothesis that intravenous administration of an nitric oxide synthase inhibitor and regional inhalation of nitric oxide can markedly alter the distribution of pulmonary blood flow during regional hypoxia. Methods Hypoxia (5% O2) was induced in the left lower lobe of the pig, and the blood flow to this lobe was measured with transit-time ultrasound. Nitric oxide was administered in the gas ventilating the hypoxic lobe and the hyperoxic lung regions with and without blockade of endogenous nitric oxide production by means of N omega-nitro-L-arginine methyl ester (L-NAME). Results Hypoxia in the left lower lobe reduced blood flow to that lobe to 27 +/- 3.9% (mean +/- SEM) of baseline values (P &lt; 0.01). L-NAME caused a further reduction in lobar blood flow in all six animals to 12 +/- 3.5% and increased arterial oxygen tension (PaO2) (P &lt; 0.01). Without L-NAME, the inhalation of nitric oxide (40 ppm) to the hypoxic lobe increased lobar blood flow to 66 +/- 5.6% of baseline (P &lt; 0.01) and, with L-NAME, nitric oxide delivered to the hypoxic lobe resulted in a lobar blood flow that was 88 +/- 9.3% of baseline (difference not significant). When nitric oxide was administered to the hyperoxic lung regions, after L-NAME infusion, the blood flow to the hypoxic lobe decreased to 2.5 +/- 1.6% of baseline and PaO2 was further increased (P &lt; 0.01). Conclusions By various combinations of nitric oxide inhalation and intravenous administration of an nitric oxide synthase inhibitor, lobar blood flow and arterial oxygenation could be markedly altered during lobar hypoxia. In particular, the combination of intravenous L-NAME and nitric oxide inhalation to the hyperoxic regions almost abolished perfusion of the hypoxic lobe and resulted in a PaO2 that equalled the prehypoxic values. This possibility of adjusting regional blood flow and thereby of improving PaO2 may be of value in the treatment of patients undergoing one-lung ventilation and of patients with acute respiratory failure.

Effects of nitric oxide synthase inhibitor on cochlear blood flow

2002 ◽  
Vol 171 (1-2) ◽  
pp. 32-42 ◽  
Author(s):  
Hideaki Hoshijima ◽  
Kazuo Makimoto ◽  
Osamu Noi ◽  
Yoshimitsu Ohinata ◽  
Hiroshi Takenaka
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Cochlear Blood Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Comparison of Forearm Vasodilatation to Substance P and Acetylcholine: Contribution of Nitric Oxide

1997 ◽  
Vol 92 (2) ◽  
pp. 133-138 ◽  
Author(s):  
David E. Newby ◽  
Nicholas A. Boon ◽  
David J. Webb
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Cell Function ◽  
Forearm Blood Flow ◽  
Venous Occlusion ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endothelial Cell Function ◽  
Synthase Inhibitor ◽  
Oxide Synthase

1. Forearm blood flow responses to incremental challenges of acetylcholine and substance P, administered via the brachial artery, were measured by venous occlusion plethysmography in eight subjects in the presence of saline, the nitric oxide synthase inhibitor, NG-monomethyl-l-arginine, and a control vasoconstrictor, noradrenaline. 2. Substance P and acetylcholine caused dose-dependent increases in forearm blood flow (P < 0.001). When separated by 30 min saline infusions, repeated responses did not undergo tachyphylaxis. 3. Noradrenaline caused a mean reduction in basal blood flow of 34–51% (P < 0.001), and augmented the percentage increases in blood flow with both substance P (P = 0.05) and acetylcholine (P = 0.03) infusions. 4. NG-Monomethyl-l-arginine caused a mean reduction in basal blood flow of 42–45% (P < 0.001) and significantly inhibited the responses to both substance P (P < 0.001) and acetylcholine (P = 0.05). 5. In comparison with saline responses, NG-monomethyl-l-arginine caused a mean inhibition of 69 ± 8% for substance P-induced vasodilatation and 40 ± 5% for acetylcholine-induced vasodilatation. However, comparing responses with those to the control vasoconstrictor noradrenaline, NG-monomethyl-l-arginine caused a mean inhibition of 81 ± 5% for substance P responses and 58 ± 3% for acetylcholine responses. Inhibition by NG-monomethyl-l-arginine of the response to substance P was significantly greater than inhibition of the response to acetylcholine (P = 0.02). 6. Hence, in healthy men, a greater proportion of the forearm vasodilatation to substance P than to acetylcholine appears to be nitric oxide-mediated. Given its greater stability, substance P may be more suitable as a pharmacological tool in the investigation of stimulated nitric oxide production and endothelial cell function.

INCREASED ORGAN BLOOD FLOW IN SEPSIS AND ITS REVERSAL WITH THE NITRIC OXIDE SYNTHASE INHIBITOR L-NAME

1993 ◽  
Vol 21 (Supplement) ◽  
pp. S280 ◽  
Author(s):  
Jörg Meyer ◽  
Joseph Stothert ◽  
Valerie Pollard ◽  
Frank Hinder ◽  
David Hemdon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Organ Blood Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

scholarly journals P2 Purinoceptor Saturation by Adenosine Triphosphate Impairs Renal Autoregulation in Dogs

1999 ◽  
Vol 10 (3) ◽  
pp. 492-498
Author(s):  
DEWAN S. A. MAJID ◽  
EDWARD W. INSCHO ◽  
L. GABRIEL NAVAR
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sodium Excretion ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitric Oxide Release ◽  
Renal Autoregulation ◽  
Mediated Effects ◽  
P2 Purinoceptors ◽  
Before And After ◽  
Synthase Inhibitor

Abstract. Recent studies have suggested a role for P2 purinoceptors on vascular smooth muscle cells in the mechanism of renal autoregulation. Experiments were performed in anesthetized dogs (n = 9) to examine renal blood flow (RBF) auto-regulatory efficiency before and after saturation of P2 purinoceptors with acute intra-arterial administration of ATP (1 mg/kg per min). Dogs were pretreated with the nitric oxide synthase inhibitor nitro-L-arginine (NLA) (50 μg/kg per min), to avoid endothelial P2 receptor-mediated effects on nitric oxide release caused by the intra-arterial ATP infusions. NLA treatment decreased RBF (5.3 ± 0.3 to 3.6 ± 0.2 ml/min per g) and sodium excretion (3.6 ± 0.4 to 0.9 ± 0.2 ml/min per g) without producing significant changes in GFR (0.92 ± 0.04 to 0.90 ± 0.06 ml/min per g) or RBF autoregulatory efficiency. ATP administration to NLA-treated dogs resulted in further decreases in RBF (2.8 ± 0.2 ml/min per g), GFR (0.58 ± 0.05 ml/min per g), and sodium excretion (0.6 ± 0.2 μmol/min per g). In addition, there was marked impairment of RBF autoregulatory efficiency during ATP infusion. The slopes of the arterial pressure-blood flow relationships at renal arterial pressures of >75 mmHg were significantly altered, from 0.003 ± 0.001 to 0.2 ± 0.002 ml/min per g per mmHg. Discontinuation of ATP infusion restored RBF autoregulatory efficiency. Norepinephrine (5 μg/kg per min) administration in these NLA-treated dogs decreased RBF (2.5 ± 0.3 ml/min per g; n = 4) to a similar extent, compared with ATP, but did not impair RBF autoregulation. These results support the hypothesis that P2 purinoceptors may be involved in mediating autoregulatory adjustments in renal vascular resistance.

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