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.

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

Ageing is associated with impairment of nitric oxide and prostanoid dilator pathways in the human forearm

2002 ◽  
Vol 102 (5) ◽  
pp. 595-600 ◽  
Author(s):  
Nivedita SINGH ◽  
Sanjay PRASAD ◽  
Donald R.J. SINGER ◽  
Raymond J. Mac ALLISTER
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Forearm Blood Flow ◽  
Area Under The Curve ◽  
Venous Occlusion ◽  
Response Curves ◽  
Age Related ◽  
Older Subjects ◽  
Synthase Inhibitor ◽  
Dose Dependent

Ageing is associated with endothelial dysfunction and increased cardiovascular risk. We assessed the activity of nitric oxide (NO) and prostaglandin pathways in older subjects. Bilateral venous occlusion plethysmography was used to measure forearm blood flow during intra-arterial infusion of the NO synthase inhibitor, NG-monomethyl-l-arginine (l-NMMA; 1, 2 and 4μmol/min), the cyclo-oxygenase inhibitor, aspirin (3, 9 and 30μmol/min), and the smooth muscle constrictor, noradrenaline (60, 120 and 240pmol/min); each dose infused for 5min. Eighteen young and 15 healthy older subjects (mean age±S.E.M., 32±1 and 65±1 years respectively) were studied. Effects of treatment were calculated from the ratio of blood flow in the infused to control arm, expressed as a percentage. Dose-response curves were compared by analysis of the area under the curve (AUC) using independent samples t test. All agents caused dose-dependent decreases in basal forearm blood flow. AUC values for noradrenaline, aspirin and l-NMMA in younger and older subjects were 162±24, 173±24 and 170±17, and 138±22, 70±22 and 89±22 respectively. Effects of aspirin and l-NMMA, but not noradrenaline, were reduced in older subjects (P = 0.004, 0.007 and 0.461 respectively). Our findings suggest a generalized abnormality of basal endothelial function in older people, with similar impairment of NO and prostanoid dilator pathways. Defects in both pathways could contribute to the development of age-related cardiovascular disease.

Nitric oxide-mediated vasodilation in human pregnancy

1997 ◽  
Vol 272 (2) ◽  
pp. H748-H752 ◽  
Author(s):  
D. J. Williams ◽  
P. J. Vallance ◽  
G. H. Neild ◽  
J. A. Spencer ◽  
F. J. Imms
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Late Pregnancy ◽  
Venous Occlusion ◽  
Maternal Circulation ◽  
Healthy Human ◽  
Nitric Oxide Synthase Inhibitor ◽  
Human Pregnancy ◽  
Oxide Synthase

The maternal circulation vasodilates during pregnancy. We investigated the contribution of nitric oxide to this vasodilatation. Using venous occlusion plethysmography, we measured the effect of nitric oxide synthase inhibition on hand blood flow during human pregnancy. We compared the response to a brachial artery infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) with the response to norepinephrine in three groups of women: nonpregnant, early pregnant (9-15 wk), and late pregnant (36-41 wk). Basal hand blood flow increased significantly during late pregnancy compared with nonpregnant and early pregnant subjects (P = 0.007). L-NMMA produced a greater reduction in hand blood flow in both pregnant groups compared with nonpregnant controls (P = 0.0003). Norepinephrine produced an attenuated response in late pregnancy compared with nonpregnant and early pregnant women (P = 0.0029). If other vascular beds respond in the same way as the hand, the gestational increase in vasoconstrictor response to L-NMMA that we observed implicates increased generation of nitric oxide in the fall of peripheral vascular resistance during healthy human pregnancy.

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
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