Effect of nitric oxide synthase inhibitors on short-term appetite and food intake in humans

1999 ◽  
Vol 276 (6) ◽  
pp. R1562-R1568 ◽  
Author(s):  
Rosalie Vozzo ◽  
Gary A. Wittert ◽  
Michael Horowitz ◽  
John E. Morley ◽  
Ian M. Chapman
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Food Intake ◽  
Animal Studies ◽  
Caloric Intake ◽  
Short Term ◽  
Double Blind ◽  
Visual Analog Scales ◽  
Oxide Synthase

Animal studies suggest that nitric oxide (NO) may be a physiological regulator of appetite; NO synthase (NOS) inhibition suppresses food intake in rats, mice, and chickens. It is not known whether NO has any effect on appetite in humans. We have used N G-monomethyl-l-arginine (l-NMMA) and N G-nitro-l-arginine methyl ester (l-NAME), both competitive, nonselective inhibitors of NOS, in two separate studies to evaluate the role of NO in the short-term regulation of appetite in humans. In study I, 13 men (18–25 yr) underwent paired studies, in randomized, double-blind fashion, after an overnight fast. l-NMMA (4 mg ⋅ kg−1 ⋅ h−1) or saline (0.9%) was infused intravenously at a rate of 40 ml/h for 1.5 h. In study II, eight men (18–26 yr) underwent three randomized, double-blind studies after an overnight fast. l-NAME (75 or 180 μg ⋅ kg−1 ⋅ h−1) or saline (0.9%) was infused intravenously at a rate of 20 ml/h for 120 min. Hunger and fullness were measured using visual analog scales; blood pressure and heart rate were monitored, and 30 min before the end of the infusion, subjects were offered a cold buffet meal. Total caloric intake and the macronutrient composition of the meal were determined. Both l-NMMA ( P = 0.052) andl-NAME ( P < 0.05; both doses) decreased heart rate, l-NMMA increased diastolic blood pressure ( P < 0.01), and l-NAME increased systolic blood pressure ( P = 0.052). Neither drug had any effect on caloric intake or sensations of hunger or fullness. Despite having significant effects on cardiovascular function in the doses used, neitherl-NMMA norl-NAME had any effect on feeding, suggesting that NO does not affect short-term appetite or food intake in humans.

scholarly journals The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1679 ◽  
Author(s):  
David Khalaf ◽  
Marcus Krüger ◽  
Markus Wehland ◽  
Manfred Infanger ◽  
Daniela Grimm
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Animal Studies ◽  
Current Data ◽  
No Production ◽  
First Pass Metabolism ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Antihypertensive Properties ◽  
Pass Metabolism

Nitric oxide (NO) is a well-known vasodilator produced by the vascular endothelium via the enzyme endothelial nitric oxide synthase (eNOS). The inadequate production of NO has been linked to elevated blood pressure (BP) in both human and animal studies, and might be due to substrate inaccessibility. This review aimed to investigate whether oral administration of the amino acids l-arginine (Arg) and l-citrulline (Cit), which are potential substrates for eNOS, could effectively reduce BP by increasing NO production. Both Arg and Cit are effective at increasing plasma Arg. Cit is approximately twice as potent, which is most likely due to a lower first-pass metabolism. The current data suggest that oral Arg supplementation can lower BP by 5.39/2.66 mmHg, which is an effect that is comparable with diet changes and exercise implementation. The antihypertensive properties of Cit are more questionable, but are likely in the range of 4.1/2.08 to 7.54/3.77 mmHg. The exact mechanism by which Cit and Arg exert their effect is not fully understood, as normal plasma Arg concentration greatly exceeds the Michaelis constant (Km) of eNOS. Thus, elevated plasma Arg concentrations would not be expected to increase endogenous NO production significantly, but have nonetheless been observed in other studies. This phenomenon is known as the “l-arginine paradox”.

Effect of systemic nitric oxide synthase inhibition on postexercise hypotension in humans

2000 ◽  
Vol 89 (5) ◽  
pp. 1830-1836 ◽  
Author(s):  
John R. Halliwill ◽  
Christopher T. Minson ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Animal Studies ◽  
Adrenergic Blockade ◽  
Regional Hemodynamics ◽  
Postexercise Hypotension ◽  
Peak Aerobic Capacity ◽  
Oxide Synthase

An acute bout of aerobic exercise results in a reduced blood pressure that lasts several hours. Animal studies suggest this response is mediated by increased production of nitric oxide. We tested the extent to which systemic nitric oxide synthase inhibition [ N G-monomethyl-l-arginine (l-NMMA)] can reverse the drop in blood pressure that occurs after exercise in humans. Eight healthy subjects underwent parallel experiments on 2 separate days. The order of the experiments was randomized between sham (60 min of seated upright rest) and exercise (60 min of upright cycling at 60% peak aerobic capacity). After both sham and exercise, subjects received, in sequence, systemic α-adrenergic blockade (phentolamine) and l-NMMA. Phentolamine was given first to isolate the contribution of nitric oxide to postexercise hypotension by preventing reflex changes in sympathetic tone that result from systemic nitric oxide synthase inhibition and to control for alterations in resting sympathetic activity after exercise. During each condition, systemic and regional hemodynamics were measured. Throughout the study, arterial pressure and vascular resistances remained lower postexercise vs. postsham despite nitric oxide synthase inhibition (e.g., mean arterial pressure afterl-NMMA was 108.0 ± 2.4 mmHg postsham vs. 102.1 ± 3.3 mmHg postexercise; P < 0.05). Thus it does not appear that postexercise hypotension is dependent on increased production of nitric oxide in humans.

Short-term and long-term blood pressure and heart rate variability in the mouse

2000 ◽  
Vol 278 (1) ◽  
pp. R215-R225 ◽  
Author(s):  
Ben J. A. Janssen ◽  
Peter J. A. Leenders ◽  
Jos F. M. Smits
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Pressure Fluctuations ◽  
Sympathetic Nerves ◽  
Pulse Interval ◽  
Control Mechanisms ◽  
Short Term ◽  
Endogenous Nitric Oxide ◽  
Short Term Variability

Knowledge on murine blood pressure and heart rate control mechanisms is limited. With the use of a tethering system, mean arterial pressure (MAP) and pulse interval (PI) were continuously recorded for periods up to 3 wk in Swiss mice. The day-to-day variation of MAP and PI was stable from 5 days after surgery. Within each mouse ( n = 9), MAP and PI varied by 21 ± 6 mmHg and 17 ± 4 ms around their respective 24-h averages (97 ± 3 mmHg and 89 ± 3 ms). Over 24-h periods, MAP and PI were bimodally distributed and clustered around two preferential states. Short-term variability of MAP and PI was compared between the resting (control) and active states using spectral analysis. In resting conditions, variability of MAP was mainly confined to frequencies <1 Hz, whereas variability of PI was predominantly linked to the respiration cycle (3–6 Hz). In the active state, MAP power increased in the 0.08- to 3-Hz range, whereas PI power fell in the 0.08- to 0.4-Hz range. In both conditions, coherence between MAP and PI was high at 0.4 Hz with MAP leading the PI fluctuations by 0.3–0.4 s, suggesting that reflex coupling between MAP and PI occurred at the same frequency range as in rats. Short-term variability of MAP and PI was studied after intravenous injection of autonomic blockers. Compared with the resting control state, MAP fell and PI increased after ganglionic blockade with hexamethonium. Comparable responses of MAP were obtained with the α-blocker prazosin, whereas the β-blocker metoprolol increased PI similarly. Muscarinic blockade with atropine did not significantly alter steady-state levels of MAP and PI. Both hexamethonium and prazosin decreased MAP variability in the 0.08- to 1-Hz range. In contrast, after hexamethonium and metoprolol, PI variability increased in the 0.4- to 3-Hz range. Atropine had no effect on MAP fluctuations but decreased those of PI in the 0.08- to 1-Hz range. These data indicate that, in mice, blood pressure and its variability are predominantly under sympathetic control, whereas both vagal and sympathetic nerves control PI variability. Blockade of endogenous nitric oxide formation by N G-nitro-l-arginine methyl ester increased MAP variability specifically in the 0.08- to 0.4-Hz range, suggesting a role of nitric oxide in buffering blood pressure fluctuations.

The effect of chronic nitric oxide synthase inhibition on blood pressure and heart rate in unrestrained pregnant rats as recorded by radiotelemetry

1999 ◽  
Vol 181 (1) ◽  
pp. 159-164 ◽  
Author(s):  
Catalin S. Buhimschi ◽  
Remzi Gokdeniz ◽  
George R. Saade ◽  
Irina A. Buhimschi ◽  
Robert E. Garfield
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Nitric Oxide Synthase ◽  
Pregnant Rats ◽  
Oxide Synthase

Hemodynamic and Electrocardiographic Effects of Short-Term Ginkgo Biloba

2003 ◽  
Vol 37 (3) ◽  
pp. 345-349 ◽  
Author(s):  
James S Kalus ◽  
Alexandria A Piotrowski ◽  
Christopher R Fortier ◽  
Xinhcun Liu ◽  
Jeffrey Kluger ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Ginkgo Biloba ◽  
Study Drug ◽  
P Wave ◽  
Short Term ◽  
Double Blind ◽  
Electrocardiographic Parameters ◽  
Time Point

OBJECTIVE: To evaluate the immediate and short-term hemodynamic and electrocardiographic effects of Ginkgo biloba (ginkgo). METHODS: Healthy volunteers were randomized to receive ginkgo 120 mg or placebo twice daily for 7 days in this prospective, double blind trial. After at least a 7-day washout period, subjects were crossed over to an additional 7 days of alternate therapy. Blood pressure, heart rate, and 12-lead electrocardiograms were evaluated immediately before (baseline), and at 1, 3, and 5 hours after observed ingestion of study drug on days 1 and 7 of therapy. Electrocardiographic parameters (P wave and QRS complex duration; PR, QT, and QTc intervals) were measured in lead II by a blinded investigator. RESULTS: Ginkgo had no effect on any of the evaluated electrocardiographic parameters at any time point on days 1 or 7. Additionally, no changes in heart rate or systolic and diastolic blood pressure were found between the groups at any time point on any evaluative day. CONCLUSIONS: Commonly used doses of Ginkgo biloba do not have any immediate or short-term effects on blood pressure, heart rate, or electrocardiographic variables in young, healthy volunteers.

Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure

2008 ◽  
Vol 294 (1) ◽  
pp. H190-H197 ◽  
Author(s):  
Jill M. Wecht ◽  
Joseph P. Weir ◽  
David S. Goldstein ◽  
Annmarie Krothe-Petroff ◽  
Ann M. Spungen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Control Group ◽  
Plasma Norepinephrine ◽  
Oxide Synthase

Direct effects of vasoactive substances on blood pressure can be examined in individuals with tetraplegia due to disruption of descending spinal pathways to sympathetic preganglionic neurons, as cervical lesions interfere with baroreceptor reflex buffering of sympathetic outflow. In this study, we assessed effects of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester (l-NAME) on mean arterial pressure, heart rate, and plasma norepinephrine concentrations in individuals with tetraplegia vs. effects shown in a neurologically intact control group. Seven individuals with tetraplegia and seven age-matched controls received, on separate visits and in the following order, placebo (30 ml normal saline) and 0.5, 1, 2, and 4 mg/kg l-NAME intravenously over 60 min. Supine hemodynamic data were collected, and blood was sampled at the end of each infusion and at 120, 180, and 240 min thereafter. l-NAME increased mean arterial pressure, and the relative increase was greater in the tetraplegia group than in the control group. Heart rate was reduced after l-NAME administration in both groups. l-NAME decreased plasma norepinephrine in the control group but not in the group with tetraplegia. These findings suggest that reflexive sympathoinhibition normally buffers the pressor response to nitric oxide synthase inhibition, an effect that is not evident in individuals with tetraplegia as a result of decentralized sympathetic vasomotor control.

Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation

2008 ◽  
Vol 104 (3) ◽  
pp. 756-760 ◽  
Author(s):  
Sebastian Strempel ◽  
Christoph Schroeder ◽  
Ruth Hemmersbach ◽  
Andrea Boese ◽  
Jens Tank ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Activity ◽  
Norepinephrine Transporter ◽  
Standing Position ◽  
Vertical Acceleration ◽  
Short Term ◽  
Double Blind ◽  
Gravitational Stress ◽  
Head Up Tilt

Sympathetically mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness. Norepinephrine transporter (NET) inhibition prevents neurally mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26 ± 1 yr, body mass index 24 ± 1 kg/m2), who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal vertical acceleration load of 3 g). NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition, blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic responses to sitting, standing, and hypergravitation all were greatly increased with NET inhibition. In contrast to our expectation, short-term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia that we observed.

Caffeine and Placebo Expectation

2007 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Yunfeng Sun ◽  
Yinling Zhang ◽  
Ning He ◽  
Xufeng Liu ◽  
Danmin Miao
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sleep Deprivation ◽  
Cognitive Performance ◽  
Cognitive Functions ◽  
Cardiovascular Regulation ◽  
Double Blind ◽  
Positive Effects ◽  
Pressure Tests ◽  
Healthy Males

Abstract. Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control); caffeine 200 mg at 00:00 (C200); placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive functions were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-C200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects on vigilance and cognitive performance.

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