Intra-arterial Infusion Of Saline Research Articles

Alpha adrenergic receptor regulation of blood flow during passive leg movement: The impact of age.

Passive leg movement (PLM) evokes a robust and transient increase in limb blood flow (LBF). The magnitude of this response is attenuated with aging and this reduction has been largely attributed to diminished nitric oxide (NO) bioavailability. Importantly, aging is also associated with heightened sympathetic activity and altered vasomotor tone, which may contribute to the age‐related reduction in PLM. Therefore, this study sought to determine the contribution of α‐adrenergic signaling to the PLM‐induced LBF response in aging. The central hypothesis is that aging is associated with sympathetically‐mediated restraint of the LBF during PLM. Following intravenous infusion of the β‐blocker propranolol, five young (24±6 yr) and five old (68±4 yr) healthy male subjects underwent PLM during intra‐arterial infusion of saline (CON; control), phenylephrine (PE; α1‐adrenergic receptor agonist) and phentolamine (PHEN; nonspecific α‐adrenergic receptor antagonist). LBF through the common femoral artery was determined second‐by‐second by Doppler ultrasound. Compared with CON, PE did not reduce baseline LBF in the young (CON: 251±11; PE: 193±18 ml/min, p=0.23) or old (CON: 265±18; PE: 239±36 ml/min, p=0.74); however, PHEN increased baseline LBF in both the young (PHEN: 725 ± 63 ml/min, p<0.01 vs. CON) and the old (PHEN: 680 ± 122 ml/min, p<0.01 vs. CON). During PLM in the young, PE reduced the peak change in LBF (ΔPeakLBF) (CON: 595±67; PE: 393±46 ml/min, p=0.038) while PHEN increased the ΔPeakLBF (827 ± 89 ml/min, p=0.02 vs. CON). In contrast, in the old, no changes in ΔPeakLBF in response to PE or PHEN were evident (CON: 342±17; PE: 311±22, PHEN: 378±65 ml/min, p=0.37 for the treatment effect). The magnitude of α‐adrenergic receptor contribution (PHEN ΔPeakLBF – PE ΔPeakLBF) was different between young and old (young: 434±97; old: 67±75 ml/min, p=0.02). The overall hyperemic response, assessed by the LBF area under the curve (LBFAUC) during PLM, was not different when comparing CON (127 ± 23 ml/min) to PE (67 ± 19 ml/min, p=0.22) nor PHEN (210 ± 31 ml/min, p=0.095) in the young; however, LBFAUC was significantly different between PE and PHEN (p=0.02). Neither PE nor PHEN altered the LBFAUC in the old (CON: 82 ± 17, PE: 65 ± 9, PHEN: 127 ± 32 ml/min, p=0.29 for the treatment effect). Although both groups exhibited robust increases in baseline LBF after adrenergic receptor inhibition, only the young demonstrated alterations to the PLM response following stimulation and inhibition of adrenergic receptors. In line with previous findings, we observed sympathetic restraint of resting LBF in both young and old individuals. However, the age related reduction in ΔPeakLBF and LBFAUC during PLM in old individuals does not appear to be associated with augmented sympathetic regulation of vasomotor tone.

Acute Peripheral Metabolic Effects of Intraarterial Leg Infusion of Somatostatin in Healthy Young Men

Evidence suggests that somatostatin not only inhibits the secretion of GH but also suppresses GH action in peripheral tissues. We tested the hypothesis that somatostatin suppresses GH activity in human skeletal muscle in vivo. Eight healthy young men (25.3 ± 2.8 yr) were studied on a single occasion after an overnight fast for 4 h [including a basal period (0-2 h) and a hyperinsulinemic euglycemic clamp (2-4 h)] during an iv GH infusion (50 ng/kg⁻¹ · min⁻¹). Each subject received an intraarterial somatostatin infusion (150 μg/h⁻¹) into one femoral artery and an intraarterial saline infusion into the contra lateral artery. The simultaneous blood samples were drawn from both femoral veins. Muscle biopsies were obtained from one leg at t = 0 and from both legs during the basal period and during the clamp. Muscle glucose uptake, signaling proteins for GH (phosphorylated signal transducer and activator of transcription-5) and insulin (phosphorylation of AS160), and expression of GH-regulated genes (IGF-I and suppressor of cytokine signaling 1-3) were measured. Somatostatin significantly increased glucose uptake measured by arteriovenous glucose difference during the basal period (P = 0.03) but not during the clamp. There was a tendency for the phosphorylation of AS160 to be higher in the somatostatin-infused leg compared with the saline leg (P = 0.055). The expression of suppressor of cytokine signaling-1 mRNA was significantly elevated in the clamp-biopsy from the saline-infused leg (P = 0.024). We concluded the following: 1) in the presence of systemic GH exposure, somatostatin increases basal glucose uptake and reduces the expression of GH-regulated genes directly in skeletal muscle; 2) this supports the concept that somatostatin suppresses GH activity in peripheral tissues, and 3) this may add to the therapeutic effects of somataostatin analogs.

The role of the α‐adrenergic receptor in the leg vasoconstrictor response to orthostatic stress

The prompt increase in peripheral vascular resistance, mediated by sympathetic alpha-adrenergic stimulation, is believed to be the key event in blood pressure control during postural stress. However, despite the absence of central sympathetic control of the leg vasculature, postural leg vasoconstriction is preserved in spinal cord-injured individuals (SCI). This study aimed at assessing the contribution of both central and local sympathetically induced alpha-adrenergic leg vasoconstriction to head-up tilt (HUT) by including healthy individuals and SCI, who lack central sympathetic baroreflex control over the leg vascular bed. In 10 controls and nine SCI the femoral artery was cannulated for drug infusion. Upper leg blood flow (LBF) was measured bilaterally using venous occlusion strain gauge plethysmography before and during 30 degrees HUT throughout intra-arterial infusion of saline or the non-selective alpha-adrenergic receptor antagonist phentolamine respectively. Additionally, in six controls the leg vascular response to the cold pressor test was assessed during continued infusion of phentolamine, in order to confirm complete alpha-adrenergic blockade by phentolamine. During infusion of phentolamine HUT still caused vasoconstriction in both groups: leg vascular resistance (mean arterial pressure/LBF) increased by 10 +/- 2 AU (compared with 12 +/- 2 AU during saline infusion), and 13 +/- 3 AU (compared with 7 +/- 3 AU during saline infusion) in controls and SCI respectively. Effective alpha-adrenergic blockade did not reduce HUT-induced vasoconstriction, regardless of intact baroreflex control of the leg vasculature. Apparently, redundant mechanisms compensate for the absence of sympathetic alpha-adrenoceptor leg vasoconstriction in response to postural stress.

Basal NO Locally Modulates Human Iliac Artery Function In Vivo

We demonstrated previously that endogenous NO influences large-artery distensibility in the ovine hindlimb. However, the role of basal NO in larger human conduit arteries is controversial. The aim of this study was to investigate whether basal production of NO, acting locally, influences iliac artery distensibility in humans. Distensibility was assessed by intra-arterial measurement of the pulse wave velocity. Eighteen subjects, free of significant coronary or iliac artery disease, were studied after diagnostic cardiac catheterization. Simultaneous pressure waveforms were recorded with a high-fidelity dual-pressure sensing catheter, placed in the common iliac artery during intra-arterial infusion of saline (baseline), glyceryl trinitrate (4 nmol/min), or NG-monomethyl-L-arginine (8 and 16 micromol/min). Drugs were infused proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath, to control for any reflex changes in flow or sympathetic activation. Velocity was calculated using the foot-to-foot methodology. Six subjects received glyceryl trinitrate and 12 NG-monomethyl-L-arginine. There was no change in velocity after infusion of glyceryl trinitrate or NG-monomethyl-L-arginine via the sheath. However, infusion of glyceryl trinitrate via the catheter significantly reduced velocity by 31.43+/-5.80% (mean+/-SEM; P<0.01; P=0.02 for comparison). Likewise, infusion of the highest dose of NG-monomethyl-L-arginine via the catheter significantly increased velocity by 27.25+/-8.20% (P=0.001; P=0.02 for comparison). Importantly, there was no change in mean arterial blood pressure throughout the studies. These data indicate that under resting conditions, local NO production modulates human iliac artery distensibility and that exogenous NO increases arterial distensibility.

Forearm blood flow in pre‐eclampsia

OBJECTIVE 1. To characterise the forearm vascular reactivity of women with pre-eclampsia in the third trimester of pregnancy and compare it with that in normal or gestational hypertensive pregnancies. 2. To document female sex steroid (oestradiol, progesterone, oestriol and betahCG) levels in the three groups of women. Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of saline and vasoactive substances: angiotensin II, sodium nitroprusside, acetylcholine and N(G)-monomethyl-L-arginine (L-NMMA). Research laboratory at St George Hospital, Kogarah, Sydney, Australia. Fifteen non-pregnant women in the follicular phase of the menstrual cycle, 15 third trimester normal pregnant women, 13 women in the third trimester with gestational hypertension and 15 women with pre-eclampsia. Changes in forearm blood flow in response to vasoactive substances. Normal pregnant women had higher baseline forearm blood flow than non-pregnant women, decreased vasodilator responses to sodium nitroprusside and reduced vasoconstrictor responses to angiotensin II. No difference in response to angiotensin II, sodium nitroprusside or L-NMMA was found among normal pregnant, pre-eclampsia or gestational hypertension women, but vasodilatory responses of pre-eclamptic women to acetylcholine were reduced compared with normal pregnant women. Higher serum progesterone levels were found in women with pre-eclampsia and gestational hypertension than in normal pregnancy. The hyperdynamic circulation of normal pregnancy is characterised by refractoriness to angiotensin II but this is not altered in pre-eclampsia. Pre-eclamptic women demonstrate a reduced vasodilator response to acetylcholine which, in the absence of any alteration in response to L-NMMA, implies that factors other than nitric oxide deficiency mediate the vasoconstriction of pre-eclampsia.

Forearm blood flow in pre-eclampsia

Objective 1. To characterise the forearm vascular reactivity of women with pre-eclampsia in the third trimester of pregnancy and compare it with that in normal or gestational hypertensive pregnancies. 2. To document female sex steroid (oestradiol, progesterone, oestriol and βhCG) levels in the three groups of women. Design Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of saline and vasoactive substances: angiotensin II, sodium nitroprusside, acetylcholine and N G-monomethyl- l-arginine ( l-NMMA). Setting Research laboratory at St George Hospital, Kogarah, Sydney, Australia. Sample Fifteen non-pregnant women in the follicular phase of the menstrual cycle, 15 third trimester normal pregnant women, 13 women in the third trimester with gestational hypertension and 15 women with pre-eclampsia. Main outcome measures Changes in forearm blood flow in response to vasoactive substances. Results Normal pregnant women had higher baseline forearm blood flow than non-pregnant women, decreased vasodilator responses to sodium nitroprusside and reduced vasoconstrictor responses to angiotensin II. No difference in response to angiotensin II, sodium nitroprusside or l-NMMA was found among normal pregnant, pre-eclampsia or gestational hypertension women, but vasodilatory responses of pre-eclamptic women to acetylcholine were reduced compared with normal pregnant women. Higher serum progesterone levels were found in women with pre-eclampsia and gestational hypertension than in normal pregnancy. Conclusion The hyperdynamic circulation of normal pregnancy is characterised by refractoriness to angiotensin II but this is not altered in pre-eclampsia. Pre-eclamptic women demonstrate a reduced vasodilator response to acetylcholine which, in the absence of any alteration in response to l-NMMA, implies that factors other than nitric oxide deficiency mediate the vasoconstriction of pre-eclampsia.

Sympathetic restraint of muscle blood flow at the onset of dynamic exercise.

Little attention has focused on sympathetic influences on skeletal muscle blood flow at the onset of exercise. We hypothesized that 1) the sympathetic nervous system constrains muscle blood flow and 2) the decline from peak blood flow is mediated by increasing sympathetic vasoconstrictor tone. Mongrel dogs (n = 7) ran on a treadmill after intra-arterial infusion of saline (control) or combined alpha(1)- and alpha(2)-adrenergic blockade (prazosin and rauwolscine). Immediate and rapid increases in hindlimb blood flow occurred at commencement of exercise with peak iliac blood flows averaging 933 +/- 79 and 1,227 +/- 90 ml/min during control and blockade conditions, respectively. At 1 min of exercise, hindlimb blood flow had decreased to 629 +/- 54 and 1,057 +/- 89 ml/min. In the absence of sympathetic vasoconstrictor tone, there was an enhanced peak blood flow at the onset of exercise. In addition, alpha-blockade attenuated the overshoot of hindlimb blood flow compared with the control condition. These data suggest that an immediate and sustained increase in sympathetic outflow restrains hindlimb blood flow at the onset of exercise and is responsible, at least in part, for an overshoot of blood flow to exercising skeletal muscle.

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

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 approximately 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 NG-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, but L-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereas L-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation that L-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.

Melatonin does not increase IOP significantly in rabbits.

New Zealand white rabbits have a circadian rhythm of intraocular pressure; pressure is higher during the dark than during the light. We explored the possibility that the dark phase increase of serum and/or ocular melatonin plays a role in regulating the rhythm of intraocular pressure. Exogenous melatonin was delivered by four routes: topical application (0.1 and 10 micrograms), intravenous injection (1 microgram), intravitreal injection (9 micrograms) and intra-arterial infusion (50 ng and 1 microgram). Melatonin delivered by these routes did not increase intraocular pressure. We also measured the concentration of melatonin in the aqueous after unilateral intra-arterial infusion to confirm that melatonin delivered by this route reached the eye. The concentration was 419 +/- 99 and 109 +/- 17 pg/ml (n = 8, p < 0.025) in the ipsilateral and contralateral eyes, respectively. The concentration of melatonin in the aqueous after intra-arterial infusion of saline was less than the sensitivity of the assay (< 16 pg/ml, n = 6). The results of these experiments indicate that melatonin does not increase IOP significantly under the experimental conditions employed in this study.

Liberation of Acetylcholine from the Perfused Human Placenta

A fresh human placenta was washed by an intra-arterial saline infusion until the fluid coming from the placenta became colorless. The wet weight having been taken, a piece weighing about 30 gm. was removed and extracted for the basal acetylcholine (hereinafter designated as a.c.) content. The placenta was supported on wire gauze fixed in the middle part of a large funnel, and perfused with a known volume (445-510 cc.) of oxygenated saline by means of a Dale-Schuster pump at a pressure of 90-100 mm. Hg. The whole outfit was kept in a small room which could be readily maintained at body temperature. At hourly intervals, the placenta was detached, weighed and a small piece removed for extraction. The perfusion-fluid was measured and 2 cc. were taken out each time for titrating its a.c.-activity. All the samples of tissue were extracted for 2 hours with 2 volumes of 96% alcohol. The different extracts and the samples of the perfusion-fluid were assayed on the same rectus-preparation.1 The influence of body-te...