Selective α2-adrenergic properties of dexmedetomidine over clonidine in the human forearm

2005 ◽  
Vol 99 (2) ◽  
pp. 587-592 ◽  
Author(s):  
Shizue Masuki ◽  
Frank A. Dinenno ◽  
Michael J. Joyner ◽  
John H. Eisenach
Keyword(s):  
Blood Flow ◽  
Young Adults ◽  
Brachial Artery ◽  
Forearm Blood Flow ◽  
Adrenergic Blockade ◽  
Norepinephrine Release ◽  
Similar Extent ◽  
Human Forearm ◽  
Before And After

We tested the hypothesis that dexmedetomidine (Dex) has greater α2- vs. α1 selectivity than clonidine and causes more α2-selective vasoconstriction in the human forearm. After local β-adrenergic blockade with propranolol, forearm blood flow (plethysmography) responses to brachial artery administration of Dex, clonidine, and phenylephrine (α1-agonist) were determined in healthy young adults before and after α2-blockade with yohimbine ( n = 10) or α1-blockade with prazosin ( n = 9). Yohimbine had no effect on phenylephrine-mediated vasoconstriction but blunted Dex-mediated vasoconstriction (mean ± SE: −41 ± 5 vs. −11 ± 2%; before vs. after yohimbine) more than clonidine-mediated vasoconstriction (−39 ± 5 vs. −28 ± 4%; before vs. after yohimbine) ( P < 0.02). Prazosin blunted phenylephrine-mediated vasoconstriction (−39 ± 4 vs. −8 ± 2%; before vs. after prazosin) but had similar effects on both Dex- (−30 ± 4 vs. −39 ± 6%; before vs. after prazosin) and clonidine-mediated vasoconstriction (−29 ± 3 vs. −41 ± 7%; before vs. after prazosin) ( P > 0.7). Both Dex and clonidine reduced deep forearm venous norepinephrine concentrations to a similar extent (−59 ± 12 vs. −55 ± 10 pg/ml; Dex vs. clonidine, P > 0.6); this effect was abolished by yohimbine and blunted by prazosin. These results suggest that Dex causes more α2-selective vasoconstriction in the forearm than clonidine. The similar vasoconstrictor responses to both drugs after prazosin might be explained by the presynaptic effects on norepinephrine release.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Exogenous NO administration and α-adrenergic vasoconstriction in human limbs

2003 ◽  
Vol 95 (6) ◽  
pp. 2370-2374 ◽  
Author(s):  
Jaya B. Rosenmeier ◽  
Sandy J. Fritzlar ◽  
Frank A. Dinenno ◽  
Michael J. Joyner
Keyword(s):  
Blood Flow ◽  
Skeletal Muscles ◽  
Forearm Blood Flow ◽  
Norepinephrine Release ◽  
Vascular Conductance ◽  
No Donor ◽  
Exercise Hyperemia ◽  
Functional Sympatholysis ◽  
Human Forearm ◽  
Forearm Vascular Conductance

Nitric oxide (NO) is capable of blunting α-adrenergic vasoconstriction in contracting skeletal muscles of experimental animals (functional sympatholysis). We therefore tested the hypothesis that exogenous NO administration can blunt α-adrenergic vasoconstriction in resting human limbs by measuring forearm blood flow (FBF; Doppler ultrasound) and blood pressure in eight healthy males during brachial artery infusions of three α-adrenergic constrictors (tyramine, which evokes endogenous norepinephrine release; phenylephrine, an α1-agonist; and clonidine, an α2-agonist). To simulate exercise hyperemia, the vasoconstriction caused by the α-agonists was compared during adenosine-mediated (>50% NO independent) and sodium nitroprusside-mediated (SNP; NO donor) vasodilation of the forearm. Both adenosine and SNP increased FBF from ∼35–40 to ∼200–250 ml/min. All three α-adrenergic constrictor drugs caused marked reductions in FBF and calculated forearm vascular conductance ( P < 0.05). The relative reductions in forearm vascular conductance caused by the α-adrenergic constrictors during SNP infusion were similar (tyramine, –74 ± 3 vs. –65 ± 2%; clonidine, –44 ± 6 vs. –44 ± 6%; P > 0.05) or slightly greater (phenylephrine, –47 ± 6 vs. –33 ± 6%; P < 0.05) compared with the responses during adenosine. In conclusion, these results indicate that exogenous NO sufficient to raise blood flow to levels simulating those seen during exercise does not blunt α-adrenergic vasoconstriction in the resting human forearm.

Effects of arm dominance and brachial artery cannulation on forearm blood flow measured by strain-gauge plethysmography

1999 ◽  
Vol 97 (5) ◽  
pp. 539-546 ◽  
Author(s):  
Adriaan M. KAMPER ◽  
Peter C. CHANG
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Intravenous Infusion ◽  
Forearm Blood Flow ◽  
Arterial Cannulation ◽  
Flow Measurements ◽  
Artery Cannulation ◽  
Before And After ◽  
Blood Flow Ratio ◽  
Arm Dominance

The human forearm model is used extensively in physiological, pharmacological and clinical investigations. Effects of arm dominance or arterial cannulation on forearm flow measurements have never been tested formally. In the present study we tested the hypotheses that left or right arm dominance or cannulation of the brachial artery do not affect forearm haemodynamic responses to physiological or pharmacological stimuli. Results obtained in 16 volunteers showed that forearm blood flow responses to physiological stimuli are comparable before and after intra-arterial cannulation in either the dominant or the non-dominant forearm. Cannulation of a forearm brachial artery has a small effect on baseline blood flow. Responses to intra-arterially infused noradrenaline (norepinephrine) were not influenced by left or right arm dominance. Intravenous infusion of noradrenaline in eight subjects resulted in small responses in forearm blood flow that were slightly asymmetrical. During the intravenous infusion of noradrenaline, forearm blood flow or the forearm blood flow ratio did not reflect the marked increase in FVR that occurred. These results support our hypotheses (a) that either arm can be used as the control or intervention arm, and (b) that intra-arterial cannulation does not affect the results of intra-arterial infusion studies.

Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans

1996 ◽  
Vol 81 (4) ◽  
pp. 1516-1521 ◽  
Author(s):  
J. K. Shoemaker ◽  
H. L. Naylor ◽  
Z. I. Pozeg ◽  
R. L. Hughson
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Forearm Blood Flow ◽  
Voluntary Contraction ◽  
Double Blind ◽  
Rate Of Increase ◽  
Forearm Exercise ◽  
Blind Manner ◽  
Exercise In Humans

Shoemaker, J. K., H. L. Naylor, Z. I. Pozeg, and R. L. Hughson. Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans. J. Appl. Physiol. 81(4): 1516–1521, 1996.—The time course and magnitude of increases in brachial artery mean blood velocity (MBV; pulsed Doppler), diameter ( D; echo Doppler), mean perfusion pressure (MPP; Finapres), shear rate (γ˙ = 8 ⋅ MBV/ D), and forearm blood flow (FBF = MBV ⋅ π r 2) were assessed to investigate the effect that prostaglandins (PGs) have on the hyperemic response on going from rest to rhythmic exercise in humans. While supine, eight healthy men performed 5 min of dynamic handgrip exercise by alternately raising and lowering a 4.4-kg weight (∼10% maximal voluntary contraction) with a work-to-rest cycle of 1:1 (s/s). When the exercise was performed with the arm positioned below the heart, the rate of increase in MBV and γ˙ was faster compared with the same exercise performed above the heart. Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) and placebo were administered orally for 2 days before two separate testing sessions in a double-blind manner. Resting heart rate was reduced in Ibu (52 ± 3 beats/min) compared with placebo (57 ± 3 beats/min) ( P < 0.05) without change to MPP. With placebo, D increased in both arm positions from ∼4.3 mm at rest to ∼4.5 mm at 5 min of exercise ( P < 0.05). This response was not altered with Ibu ( P > 0.05). Ibu did not alter the time course of MBV or forearm blood flow ( P > 0.05) in either arm position. The γ˙ was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 s of below the heart exercise ( P < 0.05). Because PG inhibition altered the time course ofγ˙ at the brachial artery, but not FBF, it was concluded that PGs are not essential in regulating the blood flow responses to dynamic exercise in humans.

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.

Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip

2000 ◽  
Vol 279 (2) ◽  
pp. H586-H593 ◽  
Author(s):  
Frank Lee ◽  
J. Kevin Shoemaker ◽  
Patrick M. McQuillan ◽  
Allen R. Kunselman ◽  
Michael B. Smith ◽  
...  
Keyword(s):  
Blood Flow ◽  
Forearm Blood Flow ◽  
Muscle Blood Flow ◽  
Reflex Responses ◽  
Muscle Ph ◽  
Before And After ◽  
Autonomic Reflex ◽  
Bier Block ◽  
Forearm Muscle ◽  
Increased Blood Flow

We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and 31P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm ( P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K+ release and H+release were both increased during exercise ( P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 ± 0.08 vs. 6.20 ± 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H+ release, presumably through a preferential recruitment of oxidative fibers.

Adenosine contributes to hypoxia-induced forearm vasodilation in humans

1999 ◽  
Vol 87 (6) ◽  
pp. 2218-2224 ◽  
Author(s):  
Urs A. Leuenberger ◽  
Kris Gray ◽  
Michael D. Herr
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Brachial Artery ◽  
Adenosine Receptors ◽  
Forearm Blood Flow ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Normal Subjects ◽  
Local Release ◽  
Forearm Vascular Resistance

In humans, hypoxia leads to increased sympathetic neural outflow to skeletal muscle. However, blood flow increases in the forearm. The mechanism of hypoxia-induced vasodilation is unknown. To test whether hypoxia-induced vasodilation is cholinergically mediated or is due to local release of adenosine, normal subjects were studied before and during acute hypoxia (inspired O210.5%; ∼20 min). In experiment I, aminophylline (50–200 μg ⋅ min−1 ⋅ 100 ml forearm tissue−1) was infused into the brachial artery to block adenosine receptors ( n = 9). In experiment II, cholinergic vasodilation was blocked by atropine (0.4 mg over 4 min) infused into the brachial artery ( n = 8). The responses of forearm blood flow (plethysmography) and forearm vascular resistance to hypoxia in the infused and opposite (control) forearms were compared. During hypoxia (arterial O2 saturation 77 ± 2%), minute ventilation and heart rate increased while arterial pressure remained unchanged; forearm blood flow rose by 35 ± 6% in the control forearm but only by 5 ± 8% in the aminophylline-treated forearm ( P < 0.02). Accordingly, forearm vascular resistance decreased by 29 ± 5% in the control forearm but only by 9 ± 6% in the aminophylline-treated forearm ( P < 0.02). Atropine did not attenuate forearm vasodilation during hypoxia. These data suggest that adenosine contributes to hypoxia-induced vasodilation, whereas cholinergic vasodilation does not play a role.

Interactions between local and reflex influences on human forearm skin blood flow

1976 ◽  
Vol 41 (6) ◽  
pp. 826-831 ◽  
Author(s):  
J. M. Johnson ◽  
G. L. Brengelmann ◽  
L. B. Rowell
Keyword(s):  
Blood Flow ◽  
Skin Blood Flow ◽  
Forearm Blood Flow ◽  
Lower Body Negative Pressure ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Vasoconstrictor Response ◽  
Human Forearm ◽  
Forearm Skin ◽  
Forearm Muscle

A three-part experiment was designed to examine interactions between local and reflex influences on forearm skin blood flow (SkBF). In part I locally increasing arm skin temperature (Tsk) to 42.5 degrees C was not associated with increases in underlying forearm muscle blood flow, esophageal temperature (Tes), or forearm blood flow in the contralateral cool arm. In part II whole-body Tsk was held at 38 or 40 degrees C and the surface temperature of one arm held at 38 or 42 degrees C for prolonged periods. SkBF in the heated arm rose rapidly with the elevation in body Tsk and arm Tsk continued to rise as Tes rose. SkBF in the arm kept at 32 degrees C paralleled rising Tes. In six studies, SkBF in the cool arm ultimately converged with SkBF in the heated arm. In eight other studies, heated arm SkBF maintained an offset above cool arm SkBF throughout the period of whole-body heating. In part III, local arm Tsk of 42.5 degrees C did not abolish skin vasoconstrictor response to lower body negative pressure. We conclude that local and reflex influences to skin interact so as to modify the degree but not the pattern of skin vasomotor response.

Effect of histamine on small and large vessel pressures in the dog foreleg

1960 ◽  
Vol 198 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Francis J. Haddy
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Direct Action ◽  
Venous Pressure ◽  
Blood Flow Rate ◽  
Systemic Arterial Pressure ◽  
Adrenergic Blockade ◽  
Interstitial Pressure ◽  
Adequate Explanation ◽  
Fast Rates

In order to determine how histamine raises small venous pressure in the dog foreleg, response of pressure during spontaneous blood flow was compared with that during constan blood flow. With spontaneous blood flow, small venous pressure rose in response to both slow and fast rates of infusion of histamine into the brachial artery. Rise of small venous pressure preceded rise of interstitial pressure. Edema appeared whenever small venous pressure exceeded 26 mm Hg for 7 minutes or more. With blood flow held constant, slow rates of infusion failed to either raise small venous pressure or produce edema. Pressure rose and edema appeared despite a constant blood flow rate when the rate of infusion was increased to values which lowered systemic arterial pressure. Pressure increase was unaffected by section of foreleg nerves but was partially abolished by adrenergic blockade. Rapid intravenous infusion during constant blood flow raised small venous pressure much less and this rise was completely abolished by adrenergic blockade. These studies indicate that low rates of infusion into the brachial artery raise small venous pressure by arteriolar dilatation whereas high rates raise this pressure both by arteriolar dilatation and venous constriction. Venous constriction probably results both from a direct action of histamine and indirectly through an adrenal discharge. The study also suggests that elevation of capillary hydrostatic pressure is an adequate explanation for histamine edema.

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