Enhanced endothelium-dependent vasodilation in patients with cirrhosis

1995 ◽  
Vol 268 (3) ◽  
pp. G459-G464 ◽  
Author(s):  
A. Albillos ◽  
I. Rossi ◽  
G. Cacho ◽  
M. V. Martinez ◽  
I. Millan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Portal Hypertension ◽  
Mean Arterial Pressure ◽  
Forearm Blood Flow ◽  
Peripheral Vasodilation ◽  
Basal Serum ◽  
Resistance Vessels ◽  
Cirrhotic Patients ◽  
Forearm Vascular Resistance

Experimental evidence indicates that an increased production of nitric oxide could play a role in the peripheral vasodilation of portal hypertension. To test this hypothesis in humans, we studied basal serum NO(2-) + NO3- levels and the response of forearm resistance vessels to increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine infused into the brachial artery of 12 cirrhotic patients and 10 controls. Forearm vascular resistance (FVR) was calculated from mean arterial pressure and forearm blood flow (FBF). Cirrhotics showed higher NO(2-) + NO3- levels (P < 0.05), higher FBF (P < 0.01), and lower FVR (P < 0.01) than controls. The reduction of FVR in response to every dose of methacholine was greater in cirrhotics than in controls; this was significant (P < 0.05) at the 3 and 10 micrograms/min doses. This response to methacholine was not modified by blockade of vascular prostacyclin. The response to nitroprusside was similar in both groups. The increase in FVR in response to every dose of phenylephrine was significantly (P < 0.01) lower in cirrhotics than in controls. In cirrhotics, a significant correlation (r = -0.81, P < 0.01) was found between the FVR response to the highest doses of methacholine and phenylephrine. In conclusion, cirrhotic patients show an enhanced endothelium-mediated vasodilation, which suggests an increased synthesis of nitric oxide. This defect may mediate the peripheral vasodilation and hyporeactivity to vasopressors of these patients.

Endothelium-derived nitric oxide mediates hypoxic vasodilation of resistance vessels in humans

1996 ◽  
Vol 271 (3) ◽  
pp. H1182-H1185 ◽  
Author(s):  
M. L. Blitzer ◽  
S. D. Lee ◽  
M. A. Creager
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Vascular Resistance ◽  
Forearm Blood Flow ◽  
Vasodilator Response ◽  
Healthy Humans ◽  
Resistance Vessels ◽  
Oxide Synthase ◽  
Forearm Vascular Resistance

Endothelium-derived nitric oxide (EDNO) contributes to basal systemic vascular resistance under normoxic conditions. The purpose of this investigation was to determine whether EDNO contributes to the regulation of limb vascular resistance during hypoxia in healthy humans. Forearm blood flow was assessed by venous occlusion plethysmography. Hypoxia was induced by delivering a mixture of N2 and O2 via a gas blender adjusted to reduce the PO2 to 50 mmHg. During hypoxia, forearm blood flow increased from 2.4 +/- 0.2 to 3.0 +/- 0.3 ml.100 ml-1.min-1 (P < 0.001), and forearm vascular resistance decreased from 38 +/- 3 to 29 +/- 3 units (P < 0.001). The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 2,000 micrograms/min intra-arterially) was administered to eight subjects. The percent increase in forearm vascular resistance after administration of L-NMMA was greater during hypoxia than normoxia (67 +/- 14 vs. 39 +/- 15%, P < 0.05). L-NMMA reduced the forearm vasodilator response to hypoxia from 27 +/- 3 to 11 +/- 5% (P = 0.01). To exclude the possibility that this attenuated response to hypoxia was a consequence of vasoconstriction and not specific for nitric oxide synthase inhibition, six subjects received intra-arterial phenylephrine. Phenylephrine did not affect the vasodilator response to hypoxia (17 +/- 3 vs. 21 +/- 6%, P = NS). It is concluded that EDNO contributes to hypoxia-induced vasodilation in the forearm resistance vessels in healthy humans.

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia

1998 ◽  
Vol 95 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Daniel GREEN ◽  
Gerry O'DRISCOLL ◽  
James M. RANKIN ◽  
Andrew J. MAIORANA ◽  
Roger R. TAYLOR
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vitamin E ◽  
Endothelial Function ◽  
Sodium Nitroprusside ◽  
Vascular Resistance ◽  
Forearm Blood Flow ◽  
Elevated Serum ◽  
Tocopherol Concentration ◽  
Forearm Vascular Resistance

1.Vitamin E administration improves endothelial function in hypercholesterolaemic animals but, generally, has not been found to do so in man. The aim of this study was to determine whether vitamin E administration improves basal or stimulated function of the nitric oxide (·NO) dilator system in patients with hypercholesterolaemia. 2.Seven subjects aged 47±3 (±S.E.M.) years with moderately elevated serum cholesterol concentrations (6.0±0.1 ;mmol/l) were given 4 weeks of placebo therapy followed by 500 i.u. of vitamin E twice daily for 4 weeks. Endothelium-dependent and -independent vasodilatation were assessed by intrabrachial infusion of acetylcholine and sodium nitroprusside, and forearm blood flow was measured by strain-gauge plethysmography. Basal ·NO function was assessed by infusion of NG-monomethyl-l-arginine. 3.Plasma α-tocopherol concentration was enhanced after administration of vitamin E (34.6±1.8 to 86.9±9.6 ;μmol/l; P< 0.001). In addition, vitamin E administration significantly increased acetylcholine-mediated vasodilatation whether the results were expressed in terms of changes in absolute forearm blood flow (P< 0.01), forearm vascular resistance (P< 0.05) or forearm blood flow ratios (P< 0.001). Similarly, absolute forearm blood flow (P< 0.05), forearm vascular resistance (P< 0.01) and forearm blood flow ratio (P< 0.01) responses to NG-monomethyl-l-arginine were augmented by vitamin E therapy. Sodium nitroprusside responses were unaltered. 4.These results indicate that 4 weeks therapy with 1000 i.u. of vitamin E daily improves basal and stimulated ·NO-related endothelial function in subjects with hypercholesterolaemia.

Is nitric oxide involved in cutaneous vasodilation during body heating in humans?

1994 ◽  
Vol 76 (5) ◽  
pp. 2047-2053 ◽  
Author(s):  
N. M. Dietz ◽  
J. M. Rivera ◽  
D. O. Warner ◽  
M. J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Forearm Blood Flow ◽  
No Synthase ◽  
Oral Temperature ◽  
Drug Infusion ◽  
Cutaneous Vasodilation

The neurotransmitter responsible for neurogenic vasodilation in human skin during body heating is unknown. We sought to determine whether the vasodilating substance nitric oxide (NO) is involved in this phenomenon. Six subjects were heated for 50 min by use of a water-perfused suit while forearm blood flow (FBF) was measured with plethysmography and skin blood flow (SkBF) was measured by the laser-Doppler method in both arms. In one forearm, NG-monomethyl-L-arginine (L-NMMA), an NO synthase blocker, was infused into the brachial artery. Bolus doses of L-NMMA (< or = 4 mg/min) for 5 min were given to blunt NO-mediated vasodilator responses to acetylcholine (ACh, 64 micrograms/min). A continuous infusion of L-NMMA (< or = 1.0 mg/min) was used during body heating to maintain NO synthase blockade. In the forearm receiving L-NMMA, FBF was 1.8 +/- 0.3 ml.100 ml-1.min-1 before drug infusion and rose to 9.5 +/- 1.3 ml.100 ml-1.min-1 with ACh. After L-NMMA infusion, FBF was 1.3 +/- 0.2 ml.100 ml-1.min-1 and rose to 2.6 +/- 0.4 ml.100 ml-1.min-1 with ACh (both P < 0.05 vs. pre-L-NMMA). Similar changes in SkBF were seen with ACh and L-NMMA, confirming that the drugs reached cutaneous vessels. With body heating, oral temperature increased by 1.2 degrees C, heart rate increased by 34 beats/min, and mean arterial pressure remained constant at approximately 75 mmHg. FBF in the treated forearm rose to 11.5 +/- 2.1 vs. 12.6 +/- 1.7 ml.100 ml-1.min-1 in the control forearm (P > 0.05, control vs. treated response).(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of forearm resistance vessels by exercise training in young men

1994 ◽  
Vol 77 (4) ◽  
pp. 1829-1833 ◽  
Author(s):  
D. J. Green ◽  
N. T. Cable ◽  
C. Fox ◽  
J. M. Rankin ◽  
R. R. Taylor
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Exercise Training ◽  
Training Program ◽  
Forearm Blood Flow ◽  
Intervention Period ◽  
Flow Response ◽  
Resistance Vessels ◽  
Human Forearm ◽  
Forearm Exercise

The aim of this study was to determine whether a 4-wk handgrip training program would elicit changes in endothelium-dependent and endothelium-independent vasodilatation in resistance vessels of the human forearm. Minimum vascular resistance after a 10-min ischemic stimulus, an index of peak vasodilator capacity, was also determined. Forearm blood flow response to the endothelium-dependent vasodilator methacholine chloride did not change over the 4-wk-intervention period either in the group undertaking training (n = 11) or in control subjects (n = 6). Similarly, the response to sodium nitroprusside was not influenced by the handgrip training program. Peak vasodilator capacity of the trained forearms significantly increased, whereas no change was evident in the untrained limbs. These results suggest that 4 wk of forearm exercise training enhances peak vasodilator capacity of the vasculature without influencing stimulated activity of the nitric oxide dilator system.

Forearm and finger blood flow responses to passive body tilts

1979 ◽  
Vol 46 (2) ◽  
pp. 288-292 ◽  
Author(s):  
Y. A. Mengesha ◽  
G. H. Bell
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Arterial Blood Pressure ◽  
Vascular Resistance ◽  
Pulse Rate ◽  
Forearm Blood Flow ◽  
Body Tilt ◽  
Finger Blood Flow ◽  
Arterial Blood ◽  
Forearm Vascular Resistance

Ten to fifteen healthy subjects, ages 18--30 yr, were used to assess the correlation of forearm blood flow with graded passive body tilts and vascular resistance and also to discern the relative effects of body tilts on finger blood flow. In the head-up tilts forearm blood flow and arterial blood pressure fell progressively, whereas forearm vascular resistance and pulse rate increased. In the head-down tilts the forearm blood flow and the arterial blood pressure increased, whereas the forearm vascular resistance and pulse rate decreased. These changes were found to be significantly correlated with the different tilt angles and with one another. In a preliminary study it was found that infrared heating of the carpometacarpal region produced finger vasodilatation similar to the forearm vasodilatation observed by Crockford and Hellon (6). However, unlike forearm blood flow, finger blood flow showed no appreciable response to either the head-up or head-down tilts. This indicates that the sympathetic tone and the volume of blood in the finger are not appreciably altered by this test procedure at least 1 min after the body tilt is assumed.

scholarly journals Effects of acetylcholine and nitric oxide on forearm blood flow at rest and after a single muscle contraction

1998 ◽  
Vol 85 (6) ◽  
pp. 2249-2254 ◽  
Author(s):  
R. W. Brock ◽  
M. E. Tschakovsky ◽  
J. K. Shoemaker ◽  
J. R. Halliwill ◽  
M. J. Joyner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Muscle Contraction ◽  
Forearm Blood Flow ◽  
Mechanical Effect ◽  
Voluntary Contraction ◽  
Single Muscle ◽  
Cuff Inflation ◽  
S Period ◽  
Echo Doppler Ultrasound

We tested the hypothesis that ACh or nitric oxide (NO) might be involved in the vasodilation that accompanies a single contraction of the forearm. Eight adults (3 women and 5 men) completed single 1-s-duration contractions of the forearm to raise and lower a weight equivalent to ∼20% maximal voluntary contraction through a distance of 5 cm. In a second protocol, each subject had a cuff, placed completely about the forearm, inflated to 120 mmHg for a 1-s period, then released as a simulation of the mechanical effect of muscle contraction. Three conditions were studied, always in this order: 1) control, with intra-arterial infusion of saline; 2) after muscarinic blockade with atropine; and 3) after NO synthase inhibition with N G-monomethyl-l-arginine (l-NMMA) plus atropine. Forearm blood flow (FBF), measured by combined pulsed and echo Doppler ultrasound, was reduced at rest with l-NMMA-atropine compared with the other two conditions. After the single contraction, there were no effects of atropine, butl-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereasl-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation thatl-NMMA reduced FBF in response to both cuff inflation and a brief contraction indicates that NO from the vascular endothelium might modulate the basal level of vascular tone and the mechanical component of the hyperemia with exercise. It is unlikely that ACh and NO from the endothelium are involved in the dilator response to a single muscle contraction.

Dilator actions of arginine in human peripheral vasculature

1991 ◽  
Vol 81 (5) ◽  
pp. 695-700 ◽  
Author(s):  
Alison Calver ◽  
Joe Collier ◽  
Patrick Vallance
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Forearm Blood Flow ◽  
Hypotensive Effect ◽  
Linear Displacement ◽  
High Dose ◽  
Free Base ◽  
Peripheral Vasculature ◽  
Arginine Hydrochloride

1. l-Arginine is the physiological precursor for the formation of endothelium-derived nitric oxide. The synthesis of nitric oxide is stereospecific: d-arginine is not a substrate for nitric oxide synthase. It is possible that the provision of excess l-arginine substrate might increase the vascular synthesis of nitric oxide. We have examined this possibility by studying the effects of local infusion of l-and d-arginine in the forearm resistance bed and the superficial dorsal hand veins of healthy subjects. 2. Drugs were either infused locally into a vein on the back of the hand and then the vein diameter was measured using a linear displacement technique, or into the brachial artery and then the forearm blood flow was measured by venous occlusion plethysmography. 3. In the superficial hand veins, l- and d-arginine free base and l- and d-arginine hydrochloride (all four preparations at a dose of 5 μmol/min) all caused a significant increase in venous diameter. The responses of the l-and d-enantiomers did not differ significantly from one another. 4. In the forearm resistance bed, l- and d-arginine free base and l-arginine hydrochloride were without effect at doses of 10 and 40 μmol/min. However, at doses of 160 μmol/min all three preparations of arginine caused a significant increase in forearm blood flow compared with control values. The responses to the three preparations of arginine did not differ significantly from one another. 5. These results show that arginine in high dose is a vasodilator in both human resistance vessels and superficial veins in vivo. The response to arginine was not stereospecific: both the l- and d-enantiomers had the same effect. The dilator effect of high-dose arginine showed neither arterio-nor veno-selectivity. 6. This suggests that the hypotensive effect of systemic infusions of l-arginine in man is mediated by peripheral vasodilatation. It is not possible to ascribe the actions of arginine supplementation in this study to activation of the l-arginine/nitric oxide pathway through the provision of excess substrate.

scholarly journals Systemic and Splanchnic Lipopolysaccharide and Endothelin-1 Plasma Levels in Liver Cirrhosis before and after Transjugular Intrahepatic Portosystemic Shunt

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Jiaxiang Meng ◽  
Qing Wang ◽  
Kai Liu ◽  
Shuofei Yang ◽  
Xinxin Fan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Transjugular Intrahepatic Portosystemic Shunt ◽  
Bacterial Translocation ◽  
Portosystemic Shunt ◽  
Before And After ◽  
Intrahepatic Portosystemic Shunt ◽  
Cirrhotic Patients

Lipopolysaccharide (LPS) and endothelin- (ET-) 1 may aggravate portal hypertension by increasing intrahepatic resistance and splanchnic blood flow. In the portal vein, after TIPS shunting, LPS and ET-1 were significantly decreased. Our study suggests that TIPS can benefit cirrhotic patients not only in high hemodynamics related variceal bleeding but also in intestinal bacterial translocation associated complications such as endotoxemia.

Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation

2001 ◽  
Vol 280 (6) ◽  
pp. H2470-H2477 ◽  
Author(s):  
Julian P. J. Halcox ◽  
Suresh Narayanan ◽  
Laura Cramer-Joyce ◽  
Rita Mincemoyer ◽  
Arshed A. Quyyumi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Human Subjects ◽  
Epoxyeicosatrienoic Acid ◽  
Healthy Human ◽  
Human Forearm ◽  
Oxide Synthase ◽  
Cytochrome P 450

The identity of endothelium-dependent hyperpolarizing factor (EDHF) in the human circulation remains controversial. We investigated whether EDHF contributes to endothelium-dependent vasomotion in the forearm microvasculature by studying the effect of K+ and miconazole, an inhibitor of cytochrome P-450, on the response to bradykinin in healthy human subjects. Study drugs were infused intra-arterially, and forearm blood flow was measured using strain-gauge plethysmography. Infusion of KCl (0.33 mmol/min) into the brachial artery caused baseline vasodilation and inhibited the vasodilator response to bradykinin, but not to sodium nitroprusside. Thus the incremental vasodilation induced by bradykinin was reduced from 14.3 ± 2 to 7.1 ± 2 ml · min−1 · 100 g−1( P < 0.001) after KCl infusion. A similar inhibition of the bradykinin ( P = 0.014), but not the sodium nitroprusside (not significant), response was observed with KCl after the study was repeated during preconstriction with phenylephrine to restore resting blood flow to basal values after KCl. Miconazole (0.125 mg/min) did not inhibit endothelium-dependent or -independent responses to ACh and sodium nitroprusside, respectively. However, after inhibition of cyclooxygenase and nitric oxide synthase with aspirin and N G-monomethyl-l-arginine, the forearm blood flow response to bradykinin ( P = 0.003), but not to sodium nitroprusside (not significant), was significantly suppressed by miconazole. Thus nitric oxide- and prostaglandin-independent, bradykinin-mediated forearm vasodilation is suppressed by high intravascular K+ concentrations, indicating a contribution of EDHF. In the human forearm microvasculature, EDHF appears to be a cytochrome P-450 derivative, possibly an epoxyeicosatrienoic acid.

scholarly journals Parathyroid Hormone's Acute Effect on Vasodilatory Function

2010 ◽  
Vol 3 ◽  
pp. CMED.S4650 ◽  
Author(s):  
P. Farahnak ◽  
L. Lind ◽  
K. Mattala ◽  
I-L. Nilsson
Keyword(s):  
Cardiovascular Disease ◽  
Blood Flow ◽  
Healthy Subjects ◽  
Forearm Blood Flow ◽  
Acute Effect ◽  
Venous Occlusion ◽  
Arterial Infusion ◽  
Resistance Vessels ◽  
Vasodilatory Function ◽  
Pth Level

Parathyroid hormone (PTH) seems to affect the risk of cardiovascular disease. The aim of the present study was to investigate PTH's acute effect on endothelial vasodilatory function in forearm resistance vessels. Ten healthy subjects underwent forearm venous occlusion plethysmography. We measured forearm blood flow at baseline and at a stable, locally increased PTH level after intra-arterial infusion of metacholine and nitroprusside. The contralateral arm served as a control. Ionized calcium (Ca++) and PTH values were normal in all subjects at baseline (1.26 ± 0.02 mM/L, 3.6 ± 1.2 pM/L). After 30 minutes of PTH infusion, the PTH level increased in the active arm (13.8 ± 4.0 pM/L P < 0.01), while the Ca++ level was unchanged (1.25 ± 0.04; mM/L). Both the PTH and the Ca++ level in the contralateral arm remained unchanged, which indicates no systemic influence. The endothelial-dependent vasodilation was inversely correlated to the Ca++ level at baseline (r = −0.75, P < 0.05) and after PTH infusion (r = −0.68, P < 0.05). The vasodilatory function was not affected during PTH-infusion.

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