Regional blood flow during exercise in humans measured by near-infrared spectroscopy and indocyanine green.

Using near-infrared spectroscopy (NIRS) and the tracer indocyanine green (ICG), we quantified blood flow in calf muscle and around the Achilles tendon during plantar flexion (1-9 W). For comparison, blood flow in calf muscle was determined by dye dilution in combination with magnetic resonance imaging measures of muscle volume, and, for the peritendon region, blood flow was measured by (133)Xe washout. From rest to a peak load of 9 W, NIRS-ICG blood flow in calf muscle increased from 2.4+/-0.2 to 74+/-5 ml x 100 ml tissue(-1) x min(-1), similar to that measured by reverse dye (77+/-6 ml x 100 ml tissue(-1) x min(-1)). Achilles peritendon blood flow measured by NIRS-ICG rose with exercise from 2.2+/-0.5 to 15.1+/-0.2 ml x 100 ml(-1) x min(-1), which was similar to that determined by (133)Xe washout (2.0+/-0.6 to 14.6+/-0.3 ml x 100 ml tissue(-1) x min(-1)). This is the first study using NIRS and ICG to quantify regional tissue blood flow during exercise in humans. Due to its high spatial and temporal resolution, the technique may be useful for determining regional blood flow distribution and regulation during exercise in humans.     

Neuropeptide Y 16-36 inhibits mucociliary activity but does not affect blood flow in the rabbit maxillary sinus in vivo.

Recent investigations have shown neuropeptide Y (NPY) to be present in the rabbit maxillary sinus, and NPY is known to be released upon sympathetic nerve stimulation. To study, in vivo, the effect on mucociliary activity and blood flow, NPY 1-36 and some of its analogues were injected intra-arterially. The effects of the Y1/Y2 agonist NPY 1-36 was compared with the ones of the Y2 agonist NPY 16-36, the Y1-agonist [Leu31,Pro34]NPY and the Y1/Y2 agonist peptide YY. Mucociliary response was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity immediately prior to challenge. The effect on blood flow was measured with laser Doppler flowmetry and expressed as a percentage of the mean blood flow during the 60 s preceding challenge. NPY 1-36 and NPY 16-36 both reduced mucociliary activity dose-dependently at equimolar dosages (0.024-1.2 nmol/kg). The greatest effect was seen after the highest dosage tested. NPY 1-36 reduced mucociliary activity by 14.6 +/- 1.8%, and NPY 16-36 by 13.2 +/- 1.4%. At the highest dosage tested the Y1 receptor agonist [Leu31,Pro34]NPY did not significantly reduce mucociliary activity, whereas PYY reduced mucociliary activity by 15.0 +/- 1.8%. Injections of NPY 16-36 had no effect on blood flow whereas NPY 1-36, [Leu31,Pro34]NPY and PYY all reduced blood flow dose-dependently. Maximal decrease was seen at the highest dosage tested and was 47.1 +/- 5.4%, 70.4 +/- 7.4% and 58.2 +/- 8.4%, respectively. These findings suggest the mucociliary effects to be mediated via Y2 receptors whereas blood flow is regulated via Y1 receptors.     

Distribution of peptidergic nerves in the choroid plexus, focusing on coexistence of neuropeptide Y, vasoactive intestinal polypeptide and peptide histidine isoleucine

Choroid plexus from rat, guinea-pig, rabbit and pig was investigated by light-microscopic immunohistochemistry and by radioimmunoassay for the presence of neuropeptides. A moderately dense supply of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), respectively, was found around blood vessels and in close relation to the secretory epithelium in both pig and rabbit, while lower densities of nerve fibers were found in rat and guinea-pig. Peptide concentrations ranged from 10-40 pmolequivalents/g (pmoleqv/g) for NPY and 0.5-6 pmoleqv/g for VIP in all four species. Peptide histidine isoleucine (PHI) immunoreactive nerve fibers were present in pig choroid plexus at a lower density than NPY and VIP but with a similar distribution. Low concentrations of substance P (0.3-3 pmoleqv/g) and calcitonin gene-related peptide (0.1-3 pmoleqv/g) were found to a varying degree in choroid plexus tissue from the different species, while immunohistochemical investigation was unable to detect any immunoreactive nerve fibers. NPY was often found to coexist with VIP and PHI in pig choroid plexus, while a lesser amount of nerve fibers showed coexistence of NPY and the noradrenaline synthetizing enzyme, dopamine-beta-hydroxylase. Surgical sympathetic denervation by excision of the superior cervical ganglion in the rabbit abolished NPY-containing nerve fibers, as revealed by immunohistochemistry, but only decreased NPY levels by one third, which may be due to different identity of the peptide being detected by the two techniques. It is concluded that NPY-containing nerve fibers have a dual origin in the choroid plexus and coexist with either noradrenaline or VIP/PHI.     

Skin blood flow in sheep: comparison of xenon-133 washout and radioactive microsphere techniques

Blood flow was measured in leg and torso skin of conscious or anesthetized sheep by using 15-micron radioactive microspheres (Qm) and the 133Xe washout method (QXe). There was a good relationship between Qm in the cutaneous compartment and QXe calculated from the fast component of the biexponential washout curves (QXe = 0.40.Qm + 6.2, r = 0.90, P less than 0.001) with QXe values substantially below those determined with microspheres. Only at low blood flow levels was there a tendency for QXe to overestimate capillary blood flow as assessed with microspheres, but at higher blood flow levels the 133Xe washout method resulted in values substantially below those determined with microspheres. The slope of the slow component of the washout curves was inversely related to the tissue-blood partition coefficient in the subcutaneous tissue (r = 0.52, P less than 0.001), indicating an influence of the amount of subcutaneous fat on the washout rate. QXe calculated from the slow component of the washout curves was not significantly correlated with Qm in the subcutaneous compartment (r = 0.19, P greater than 0.10). In leg skin with dilated arteriovenous anastomoses, QXe was generally higher than in torso skin and leg skin with constricted arteriovenous anastomoses, indicating that shunt blood flow increases the washout of 133Xe.     

Effects of cardiac oscillations and lung volume on acinar gas mixing during apnea

We evaluated the importance of cardiogenic gas mixing in the acini of 13 dogs during 2 min of apnea. 133Xe (1-2 mCi in 4 ml of saline) was injected into an alveolar region through an occluded pulmonary artery branch, and washout was measured by gamma scintillation scanning during continued occlusion or with blood flow reinstated. The monoexponential rate constant for Xe washout (XeW) was -0.4 +/- 0.08 (SE) min-1 at functional residual capacity (FRC) with no blood flow in the injected region. It decreased by more than half at lung volumes 500 ml above and 392 ml below FRC. With intact pulmonary blood flow, XeW was -1.0 +/- 0.08 (SE) min-1 at FRC, and it increased with decreasing lung volume. However, if calculated Xe uptake by the blood was subtracted from the XeW measured with blood flow intact, resulting values at FRC and at FRC + 500 ml were not different from XeW with no blood flow. Reasonable calculation of Xe blood uptake at 392 ml below FRC was not possible because airway closure, increased shunt, and other factors affect XeW. After death, no significant XeW could be measured, which suggests that XeW caused by molecular diffusion was small. We conclude that 1) the effect of heart motion on the lung parenchyma increases acinar gas mixing during apnea, 2) this effect diminishes above or below FRC, and 3) there is probably no direct effect of pulmonary vascular pulsatility on acinar gas mixing.     

Blood flow in exercising muscles by xenon clearance and by microsphere trapping

The accuracy of muscle blood flow measurement by the 133Xe clearance method (QXe) was assessed against direct venous outflow (Qv) and microsphere trapping flow (Q mu) determinations in isolated perfused dog gastrocnemius both at rest and during graded stimulation [O2 consumption (VO2) up to 12 ml X 100 g-1 X min-1] and in the gastrocnemius, vastus lateralis, and triceps of intact dogs at rest and while running on a treadmill at varied speeds up to maximum VO2. In 29 measurements performed in 11 isolated muscles, Q mu was in good agreement with Qv at rest and at all stimulation levels (Q mu/Qv = 1.0; r = 0.98). 133Xe clearance yielded much lower blood flows than the venous outflow and the microsphere trapping methods. In 43 measurements in 11 muscles, the mean QXe/Qv ratio was 0.57 +/- 0.03 (SE), independent of blood flow. Similarly, in 65 measurements in 2 intact dogs, the mean QXe/Q mu ratio in all tested muscles was 0.49 +/- 0.02 (SE), independent of blood flow. These results show that the 133Xe clearance method considerably underestimates blood flow in dog muscles.     

Clinical evidence for myocardial derecruitment downstream from severe stenosis: pressure-flow control interaction

To verify the interaction between coronary pressure (CP) and blood flow (CBF) control, we studied nine candidates for angioplasty of an isolated lesion of the left anterior descending coronary artery [i.e. , percutaneous transluminal coronary angioplasty (PTCA)]. CBF (i.e., flow velocity x coronary cross-sectional area at the Doppler tip) and CP were monitored during washout of 2-5 mCi of (133)Xe after bolus injection into the left main artery before and after PTCA. Xe mean transit time (MTT) was calculated as the area under the time-activity curve, acquired by a gamma camera, divided by the dose obtained from a model fit of the Xe curve in the anterior wall. CBF response to intracoronary adenosine (2 mg) was also assessed. PTCA increased baseline CBF (from 14.5 +/- 9.4 to 20 +/- 8 ml/min, P < 0.01), coronary flow reserve (from 1.52 +/- 0.24 to 2.33 +/- 0.8, P < 0.01), and CP (from 64 +/- 9 to 100 +/- 10 mmHg, P < 0.05). MTT decreased from 89 +/- 32 to 70 +/- 19 s (P < 0.05) after PTCA; however, MTT and CBF changes were not correlated (r = -0.09, not significant). Inasmuch as MTT is the ratio of distribution volume to CBF, MTT x CBF was used as an index of perfused myocardial volume. Volume increased after PTCA from 23 +/- 18 to 56 +/- 30 ml. A direct correlation was observed between the percent increase in distal CP and percent increase in perfused volume (r = 0.91, P < 0.01). Thus low CP was not associated with exhaustion of flow reserve but, rather, with reduction of perfused myocardial volume. These data suggest that, in the presence of a severe coronary stenosis, derecruitment of vascular units occurs that is proportional to the decrease in driving pressure. Residual perfused units maintain a vasomotor tone, thus explaining the paradoxical persistence of coronary reserve.     

Neuropeptide Y immunoreactivity in the mammalian liver: pattern of innervation and coexistence with tyrosine hydroxylase immunoreactivity

Summary The distribution of nerve fibers displaying neuropeptide Y immunoreactivity in relationship to the catecholaminergic innervation of rat, guinea pig, and rabbit liver was investigated by single- and double-label immunofluorescence methods. In all three species, neuropeptide Y-immunoreactive fibers are prominent in association with the vasculature, biliary pathway, and stromal compartment. The neuropeptide Y innervation of the parenchyma, on the other hand, differs among the three species in term of density. It is quite sparse in the rat and rabbit, particularly in the former species. In the guinea pig liver, numerous single, varicose neuropeptide Y-containing nerve fibers innervate the hepatic parenchyma; often, thin processes surround single hepatocytes and lie close to sinusoids. The immunoreactive pattern of tyrosine hydroxylase, a marker for catecholaminergic neurons and fibers, is comparable to that of neuropeptide Y. Most neuropeptide Y-containing nerve fibers also contain tyrosine hydroxylase immunoreactivity, in all three species, with the exception of the rabbit parenchyma, where a substantial proportion of catecholaminergic fibers lack immunoreactivity for neuropeptide Y. Finally, systemic administration of the sympathetic neurotoxin, 6-hydroxydopamine, in rats and guinea pigs resulted in virtually complete elimination of both neuropeptide Y- and tyrosine hydroxylase-immunoreactive fibers. These findings are consistent with the hypothesis that neuropeptide Y-containing nerve fibers form a subpopulation of the sympathetic innervation of the mammalian liver, which is likely to originate from prevertebral sympathetic ganglia.     

Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers

Neuropeptide Y (NPY)-immunoreactive nerve fibers were numerous around arteries and few around veins. NPY probably co-exists with noradrenaline in such fibers since chemical or surgical sympathectomy eliminated both NPY and noradrenaline from perivascular nerve fibers and since double staining demonstrated dopamine-beta-hydroxylase, the enzyme that catalyzes the conversion of dopamine to noradrenaline, and NPY in the same perivascular nerve fibers. Studies on isolated blood vessels indicated that NPY is not a particularly potent contractile agent in vitro. NPY greatly enhanced the adrenergically mediate contractile response to electrical stimulation and to application of adrenaline, noradrenaline or histamine, as studied in the isolated rabbit gastro-epiploic and femoral arteries. The potentiating effect of NPY on the response to electrical stimulation is probably not presynaptic since NPY affected neither the spontaneous nor the electrically evoked release of [3H]noradrenaline from perivascular sympathetic nerve fibers.     

A heterogeneous tissue model for measurement of regional blood perfusion in the myocardium using inert gas isotopes

Inert gas isotopes are finding increasing application in the measurement of blood perfusion in the capillary beds of muscle, especially the myocardium. When measuring blood perfusion of the myocardium, washout curves are first produced by precordial monitoring of isotope activity following intracoronary artery injection of an inert gas isotope dissolved in saline. The washout curve data are then applied to a mathematical model to yield blood perfusion rate. Present models for this purpose either ignore any diffusive effects of gas movement (Kety-Schmidt model), or diffusive effects are accounted for by weighting the calculated perfusion value (Zierler's height-over-area technique). A new model is described here for convective and diffusive movement of an inert, nonpolar gas in myocardial tissue. A digital computer simulation of the model equations is used both to simply the model and to show agreement between the model response and experimental ¹³³Xe washout curves from normal and infracted canine hearts. The model assumes that the tail of the washout curves (portion after roughly 1.5 minutes) is caused by a heterogeneous, diffusion-limited tissue structure. The model provides two parameters which can be adjusted to washout curve data using model-matching techniques. These are perfusion rate, and a parameter which is an index of the diffusive nature of the particular myocardial area under study.     

Nitric oxide inhibition of renal vasoconstrictor responses to sympathetic cotransmitters in the pig in vivo.

The object of the present study was to investigate the involvement of nitric oxide (NO) in the regulation of renal vasoconstrictor responses to sympathetic nerve activation, and each of the known sympathetic cotransmitters separately, in the pig in vivo. Renal vasoconstrictor responses were elicited by sympathetic nerve stimulation, the alpha(1)-adrenoceptor agonist phenylephrine (10 nmol kg(-1), injected iv), neuropeptide Y (NPY, 120 pmol kg(-1), iv) acting on the NPY Y(1) receptor, and the stable ATP-analogue alpha,beta-methylene ATP (mATP, 10 nmol kg(-1)) presumably acting on the P2X(1) purinoceptor. Infusion of the NO-donor sodium nitroprusside, at a dose (0.1 mg kg(-1) h(-1), iv) that elevated renal blood flow (by 14 +/- 7%) and lowered mean arterial pressure (by 30 +/- 5%), inhibited renal vasoconstrictor responses to sympathetic nerve stimulation, phenylephrine, and NPY, but not to mATP. In contrast, injection of the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, at a dose (10 mg kg(-1), iv) that lowered renal blood flow (by 47 +/- 4%) and elevated mean arterial pressure (by 28 +/- 8%), potentiated the renal vasoconstriction evoked by sympathetic nerve stimulation, phenylephrine, and NPY, but not mATP. It is concluded that endogenous NO may function as an inhibitory modulator of vasoconstrictor responses to the sympathetic cotransmitters norepinephrine and NPY. In contrast, NO seems not to modify vasoconstrictor responses to the sympathetic cotransmitter ATP, a discrepancy that may be due to differences in the types of receptors and intracellular effector mechanisms.     

Changes of regional myocardial blood flow during and after acute focal experimental ischaemia.

The regional blood flow through the myocardium of the left ventricle was measured in 11 dogs after ligation of the left anterior descending coronary artery, by means of a local injection of 133Xe depot and precordial detection of its washout 2 hours after ligation. Immediately after ligation the blood flow in the ischaemic area declined considerably but at the same time there was a significant increase of blood flow in the non-ischaemic left ventricular myocardium. The regional flow in the ischaemic and non-ischaemic area increased insignificantly for 2 hrs. These changes were not due to alterations in coronary artery pressure, as the mean arterial pressure declined significantly during the first hour. After temporary ischaemia by ligation of the left anterior descending coronary artery for 2--4 minutes, an intensive reactive hyperaemia developed in the ischaemic region (the blood flow reached 221% of control values on the average) which was the more intensive, the greater the drop of blood flow in the ischaemic area after ligation.     

The validity of different methods of analysis of 133Xe washout curves for the determination of lung function

The influence of different mathematical methods on the analysis of ¹³³Xe washout data, used in the assessment of lung function in the pig, were investigated. When the data were fitted using a bi-exponential or a bi-exponential plus a constant type equation, neither the two clearance rate constants nor the overall 50% clearance time were found totally appropriate for the study of lung function. A new two compartmental model for the in vivo clearance of ¹³³Xe is proposed. The model assumes the whole blood as one compartment and the lung, including the pulmonary blood, as the second compartment. This suggests that the curvature of the xenon clearance curve is the result of recording the summation of the activities from the alveoli and the pulmonary blood and not, as previously described, due to the existence of two different sub-populations of alveoli.     

Effect of spaceflight on the subcutaneous venoarteriolar reflex in the human lower leg.

Whenever the legs are lowered in humans, a venoarteriolar reflex is activated by the hydrostatic distension of the venules. Through local axon reflexes, the adjacent arterioles are contracted to decrease blood flow and prevent formation of edema. Because the venoarteriolar reflex is activated by gravity, we tested the hypothesis that long-term weightlessness would attenuate it. The reduction in subcutaneous blood flow was measured by the (133)Xe washout technique just proximal to the ankle joint in dependent lower legs of eight supine astronauts, where the knee joint was passively bent by 90 degrees . The measurements were conducted before spaceflight and 3-6 h on landing following 4-6.5 mo in space. Activation of the venoarteriolar reflex reduced subcutaneous blood flow by 37 +/- 9% (P = 0.016) before flight and by 64 +/- 8% (P < 0.001) following landing with no statistical significant difference between the two reductions (P = 0.062). Therefore, our results show that the venoarteriolar reflex is not attenuated by weightlessness and therefore does not need the everyday stimulus of gravity to maintain efficiency.     

TH and NPY in sympathetic neurovascular cultures: role of LIF and NT-3

The sympathetic nervous system is an important determinant of vascular function. The effects of the sympathetic nervous system are mediated via release of neurotransmitters and neuropeptides from postganglionic sympathetic neurons. The present study tests the hypothesis that vascular smooth muscle cells (VSM) maintain adrenergic neurotransmitter/neuropeptide expression in the postganglionic sympathetic neurons that innervate them. The effects of rat aortic and tail artery VSM (AVSM and TAVSM, respectively) on neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were assessed in cultures of dissociated sympathetic neurons. AVSM decreased TH (39 +/- 12% of control) but did not affect NPY. TAVSM decreased TH (76 +/- 10% of control) but increased NPY (153 +/- 20% of control). VSM expressed leukemia inhibitory factor (LIF) and neurotrophin-3 (NT-3), which are known to modulate NPY and TH expression. Sympathetic neurons innervating blood vessels expressed LIF and NT-3 receptors. Inhibition of LIF inhibited the effect of AVSM on TH. Inhibition of neurotrophin-3 (NT-3) decreased TH and NPY in neurons grown in the presence of TAVSM. These data suggest that vascular-derived LIF decreases TH and vascular-derived NT-3 increases or maintains NPY and TH expression in postganglionic sympathetic neurons. NPY and TH in vascular sympathetic nerves are likely to modulate NPY and/or norepinephrine release from these nerves and are thus likely to affect blood flow and blood pressure. The present studies suggest a novel mechanism whereby VSM would modulate sympathetic control of vascular function.     

Innervation of the cat pineal gland by neuropeptide Y-immunoreactive nerve fibers: an experimental immunohistochemical study

An immunohistochemical study of the cat pineal gland was performed using a rabbit polyclonal antibody directed against neuropeptide Y (NPY) and an antibody directed against the C-terminal flanking peptide of neuropeptide Y (CPON). Numerous NPY- and CPON-immunoreactive (IR) nerve fibers were demonstrated throughout the gland and in the pineal capsule. The number of IR nerve fibers in the capsule was high and from this location fibers were observed to penetrate into the gland proper via the pineal connective tissue septa, often following the blood vessels. From the connective tissue septa IR fibers intruded into the parenchyma between the pinealocytes. Many IR nerve fibers were observed in the pineal stalk and in the habenular as well as the posterior commissural areas. The number of NPY/CPON-IR nerve fibers in pineal glands from animals bilaterally ganglionectomized two weeks before sacrifice was low. The source of most of the extrasympathetic NPY/CPONergic nerve fibers is probably the brain from where they enter the pineal via the pineal stalk. However, an origin of some of the fibers from parasympathetic ganglia cannot be excluded due to the presence of a few IR fibers in the pineal capsule of ganglionectomized animals. It is concluded that the cat pineal is richly innervated with NPYergic nerve fibers mostly of sympathetic origin. The posttranslational processing of the NPY promolecule results in the presence of both NPY and CPON in intrapineal nerve fibers.     

Calf blood flow during prolonged tilt in idiopathic dilated cardiomyopathy and after cardiac transplantation

In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief head-up tilt that appears to normalize after transplantation (HTX) may be present during prolonged observation also. Therefore, we studied the effect of prolonged (30 min) 50 degrees head-up tilt on calf skeletal muscle blood flow measured by the local (133)Xe washout method in CHF and after HTX and in patients with the presence vs. absence of native right atrium (+PNA and -PNA, respectively). During brief head-up tilt, skeletal muscle blood flow increased 13 +/- 42% in 9 severe CHF patients in contrast to a -28 +/- 22% decrease (P < 0.01) in 11 control subjects, -24 +/- 30% decrease in 15 moderate CHF patients (P < 0.05), -25 +/- 14% decrease in 12 patients with recent HTX (P < 0.01), and -21 +/- 24% decrease in 8 patients with distant HTX (P = 0.06). However, during sustained tilt, blood flow declined to similar levels of that in the other groups in severe CHF. HTX -PNA vs. +PNA showed blunted skeletal muscle vasomotor control (P < 0.05) and a higher systolic blood pressure (139 +/- 14 vs. 125 +/- 15 mmHg, P < 0.05) and heart rate (92 +/- 10 vs. 83 +/- 8 beats/min, P < 0.05). Thus paradox vasodilatation of calf skeletal muscle in severe CHF is present only during brief but not prolonged tilt. This may be one explanation of the rare presence of orthostatic intolerance in CHF and implies only a minor possible role for the abnormality in edema pathogenesis. Removal of all right atrium in HTX has an important hemodynamic impact that may possibly affect later clinical outcome.     

AAV mediated expression of anti-sense neuropeptide Y cRNA in the arcuate nucleus of rats results in decreased weight gain and food intake

Neuropeptide Y (NPY) is the most potent stimulant of feeding when administered by intracerebroventricular injection. Despite this, there is conflicting evidence as to its importance in the regulation of daily food intake and energy balance. It has been suggested that whilst it is important in the response to starvation it has little role in the regulation of daily food intake. To investigate the role of NPY in the regulation of food intake, anti-sense cRNA to NPY was expressed in the arcuate nucleus of adult male rats. The anti-sense NPY (AS-NPY) construct was initially tested in vitro and there was a decrease of approximately 50% in NPY release from anti-sense treated cells compared to controls (16.3 +/- 2.0 fmol/L [AS-NPY] vs 37.3 +/- 7.7 fmol/L [control], mean +/- SEM p < 0.05). NPY release from hypothalamic explants from anti-sense injected animals was decreased by over 50% compared to those from controls at both 15 and 20 days after AAV injection (15 days 42% +/- 6.5% [AS-NPY] vs 100% +/- 36% [control], 20 days 41% +/- 6% [AS-NPY] vs 100% +/- 27% [control] mean+/-SEM, p < 0.05). In a study lasting for 50 days, weight gain was significantly lower in anti-sense injected animals from day 16 (day 16: 6.25 +/- 1.10 g [AS-NPY] vs 9.42 +/- 0.65 g [control] mean +/- SEM, p < 0.05) and remained so until the end of the study when they had gained approximately 40% less weight than controls (day 50: 52.0 +/- 9.6 g [AS-NPY] vs 82.0 +/- 6.3 g [control] mean +/- SEM, p < 0.01). Cumulative food intake was significantly lower in the anti-sense injected animals from day 23 (day 23: 225.8 +/- 1.9 g [AS-NPY] vs 250.6 +/- 8.7 g [control], mean +/- SEM, p < 0.05) and remained so until the end of the study (day 50: 834.5 +/- 14.8 g [AS-NPY] vs 926.0 +/- 31.7 g [control], mean +/- SEM, p < 0.05). Similarly mean daily food intake was also reduced in the anti-sense injected animals (days 7-14: 24.9 +/- 0.4 g/day [AS-NPY] vs 27.2 +/- 0.4 g/day [control], mean +/- SEM, p < 0.01). These data are supportive of a role for NPY in the regulation of daily food intake as well as in response to starvation.     

Effect of renal vasodilatation on intrarenal blood flow distribution

Total renal blood flow (TRBF) and its intrarenal and intracortical distribution were measured before and during renal vasodilatation induced by acetylcholine infusion using the 133Xe washout, 86Rb uptake and radioactive microspheres distribution techniques. A good agreement was observed between TRBF calculated from 133Xe washout and measured with the electromagnetic flowmeter (FM). 86Rb-TRBF was lower than FM-TRBF and, due to the progressive reduction of renal 86Rb uptake, the difference increased with the increase of flow. With the alteration of TRBF the intrarenal distribution of 86Rb uptake did, however, not change significantly and, accordingly there was no redistribution of RBF either between the cortex and medulla, or among the individual cortical zones. The intracortical distribution of labelled microspheres showed, however, moderate flow dependent changes: with the rise of TRBF, due probably to the reduction of the steric hindrance, the estimated fractional perfusion of the inner cortical zones increased. The sum of the per cent 86Rb content of the innermost cortical zone (C4) and of the medulla exceeded the per cent microsphere content of zone C4. It is concluded that the medulla is perfused not exclusively with blood flowing from the juxtamedullar glomeruli. The regional flow values obtained from the 133Xe curves are not comparable with the results obtained by other methods and cannot be attributed to well defined areas of the kidney.     

Nocturnal variations in human lower leg subcutaneous blood flow related to sleep stages.

Nocturnal subcutaneous adipose tissue blood flow rate was measured in the lower legs of 10 normal human subjects together with systemic arterial blood pressure, heart rate, and registration of sleep stages under ambulatory conditions. The 133Xe washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used for measurement of blood flow rates. The sleep recordings were performed with a portable computerized sleep analysis system. In accordance with the results of previous studies, a hyperemic blood flow rate phase (mean increase 140%) for 100 min was observed approximately 60 min after the subjects went to bed. The moment of onset of the hyperemic phase was closely related to the moment of onset of the first episode of deep sleep (stages 3 and 4). There was a significant (P < 0.01) overrepresentation of deep sleep in the hyperemic phase compared with adjacent phases, and rapid-eye-movement sleep predominantly occurred in the latter part of the night, when the subcutaneous blood flow rate was stable. The results of the present study are in accordance with current theories of the interrelationship between the thermoregulatory and the arousal state control systems and, thus, might suggest that the nightly subcutaneous hyperemia represents a thermoregulatory effector mechanism.