Elevated renal perfusion pressure does not contribute to natriuresis induced by isotonic saline infusion in freely moving dogs

The study was designed to determine to what extent moderate elevation of renal perfusion pressure (RPP) via the mechanism of 'pressure natriuresis' contributes to the natriuresis induced by acute i.v. saline loading. Nine Beagle dogs maintained on ample sodium intake (5.5 mmol (kg body mass)⁻¹ day⁻¹) were chronically equipped with an aortic occluder to servocontrol RPP, a bladder catheter to measure renal function, and catheters for measurement of RPP and mean arterial blood pressure (MABP). A swivel system allowed free movement in the kennel during experiments. Isotonic saline loading (500 ml in 100 min) was studied as follows: with and without servocontrol of RPP, and these two protocols repeated in the presence of angiotensin-converting enzyme inhibition (ACEI, Enalapril, 2 mg (kg body mass)⁻¹). Saline loading increased MABP by about 12 mmHg and sodium excretion from about 28 μmol min⁻¹ up to about 350 μmol min⁻¹. Without ACEI, servocontrol of RPP at 10% below control 24 h MABP slightly delayed the onset of the saline-induced natriuresis, but did not reduce peak sodium excretion or cumulative sodium excretion. The slight delay most probably resulted from pressure-controlled renin release because, with ACEI, servocontrol of RPP did not delay or reduce the saline-induced natriuresis. In conclusion, pressure natriuresis does not contribute to the natriuresis following acute saline loading.     

Renal, cardiovascular and endocrine responses of fetal sheep at 0.8 of gestation to an infusion of amino acids

Amino acid infusions increase renal blood flow (RBF) and glomerular filtration rate (GFR) and stimulate tubular reabsorption in adults. To characterize the effects of amino acids on fetal renal haemodynamics, tubular sodium reabsorption, acid-base homeostasis and plasma renin levels, 11 chronically catheterized fetal sheep aged 121 ± 1 days (term ∼150 days) were infused i.v for 4 h with alanine, glycine, proline and serine (0.1, 0.1, 0.06 and 0.06 mmol min⁻¹, respectively) in 0.15 m saline at 0.165 ml min⁻¹. Eight control fetuses were given saline. During amino acid infusion, plasma amino acid levels increased up to 20-fold (   P < 0.005  ). GFR increased by 50 ± 8 % (   P < 0.001  ); there was only a small transient increase in RBF. Proximal fractional sodium reabsorption fell from 74.6 ± 2.9 to 55.5 ± 5.4 % (   P < 0.005  ). Distal sodium delivery increased, but a smaller percentage of this distal sodium load was reabsorbed (   P < 0.005  ). Thus fractional sodium reabsorption fell from 95.5 ± 0.9 to 81.4 ± 2.0 % (   P < 0.005  ). There was a large diuresis, natriuresis, kaliuresis and increase in osmolar excretion (   P < 0.005  ). Plasma sodium and chloride concentrations fell (   P < 0.005  ). Plasma osmolality did not change. Plasma renin levels fell (   P < 0.05  ), cortisol levels increased (   P < 0.05  ), and there was a compensated metabolic acidosis. Thus the fetal sheep kidney demonstrated a remarkable functional capacity to respond to amino acid infusion. The increase in filtration fraction and the lack of an increase in RBF suggest that efferent arteriolar vasoconstriction occurred, a very different response from the renal vasodilatation seen in adult animals.     

Renal and hormonal responses to atrial natriuretic peptide infusions in goats on high and low sodium intake

Synthetic atrial natriuretic peptide (ANP) was infused intravenously (1 microgram min-1; 60 min) in five goats during two series of experiments. For at least 4 weeks before the ANP infusions the goats received either no salt supplementation (= low sodium diet), or were given 16 g NaCl mixed with the food each day (Na = 274 mmol day-1; high sodium intake). The goats were changed between the treatments at random. ANP infusions caused diuresis, natriuresis and haemoconcentration during both diets. The urinary Na excretion increased about four-fold during the high sodium intake, and about 10 times during the low sodium intake. The urinary K excretion increased significantly during the low sodium diet, but decreased slightly during the high sodium intake. During both diets the K excretion became significantly lowered after the infusions. The mean glomerular filtration rate (GFR) was generally lower during the low sodium diet, but increased significantly during ANP infusions on both diets. The GFR returned to baseline immediately after the infusions, in contrast to urine flow and urinary Na excretion. Renal free water clearance increased slightly at the end of the infusion during the low sodium diet, but did not change during the high salt diet. Plasma renin activity (PRA) and plasma aldosterone concentration fell during ANP infusions in goats on the low sodium intake, but did not change significantly during the high sodium diet. These results indicate that the diuresis and natriuresis observed during intravenous ANP infusions in goats are mainly due to increased GFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by l -NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control, combined blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During control incremental knee extension exercise, mean blood flow in the quadriceps muscles rose from 10 ± 0.8 ml (100 ml tissue)⁻¹ min⁻¹ at rest to 124 ± 19, 245 ± 24, 329 ± 24 and 312 ± 25 ml (100 ml tissue)⁻¹ min⁻¹ at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 ± 0.5 ml (100 ml tissue)⁻¹ min⁻¹ at rest, and 100 ± 13, 163 ± 21, 217 ± 23 and 256 ± 28 ml (100 ml tissue)⁻¹ min⁻¹ at 15, 30, 45 and 60 W, respectively ( P < 0.05 vs. control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n= 6). ANP (2 μrg min^-1), ANGII (0.5 μg min^-1), or ANGII + ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5–10 mmHg both in pregnancy and in non-pregnancy. When ANGII + ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 μmol min^-1in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 μmol min^-1in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats.

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n = 6). ANP (2 micrograms min-1), ANGII (0.5 microgram min-1), or ANGII+ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5-10 mmHg both in pregnancy and in non-pregnancy. When ANGII+ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 mumol min-1 in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 mumol min-1 in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Nitric oxide inhibition and the impact on renal nerve-mediated antinatriuresis and antidiuresis in the anaesthetized rat

The contribution of nitric oxide (NO) to the antinatriuresis and antidiuresis caused by low-level electrical stimulation of the renal sympathetic nerves (RNS) was investigated in rats anaesthetized with chloralose–urethane. Groups of rats, n = 6, were given i.v. infusions of vehicle, l -NAME (10 μg kg⁻¹ min⁻¹), 1400W (20 μg kg⁻¹ min⁻¹), or S -methyl-thiocitrulline (SMTC) (20 μg kg⁻¹ min⁻¹) to inhibit NO synthesis non-selectively or selectively to block the inducible or neuronal NOS isoforms (iNOS and nNOS, respectively). Following baseline measurements of blood pressure (BP), renal blood flow (RBF), glomerular filtration rate (GFR), urine flow ( UV ) and sodium excretion ( U _Na V ), RNS was performed at 15 V, 2 ms duration with a frequency between 0.5 and 1.0 Hz. RNS did not cause measurable changes in BP, RBF or GFR in any of the groups. In untreated rats, RNS decreased UV and U _Na V by 40–50% (both P < 0.01), but these excretory responses were prevented in l -NAME-treated rats. In the presence of 1400W i.v. , RNS caused reversible reductions in both UV and U _Na V of 40–50% (both P < 0.01), while in SMTC-treated rats, RNS caused an inconsistent fall in UV , but a significant reduction ( P < 0.05) in U _Na V of 21%. These data demonstrated that the renal nerve-mediated antinatriuresis and antidiuresis was dependent on the presence of NO, generated in part by nNOS. The findings suggest that NO importantly modulates the neural control of fluid reabsorption; the control may be facilitatory at a presynaptic level but inhibitory on tubular reabsorptive processes.     

Organization of the central control of muscles of facial expression in man

The capacity of the vascular endothelium locally to release tissue-type plasminogen activator (t-PA) is critical for effective endogenous fibrinolysis. We determined the influence of ageing and regular aerobic exercise on the net release of t-PA across the human forearm in vivo using both cross-sectional and intervention approaches. First, we studied 62 healthy men aged 22-35 or 50-75 years of age who were either sedentary or endurance exercise-trained. Net endothelial release rates of t-PA were calculated as the product of the arteriovenous concentration gradient and forearm plasma flow to intra-arterial bradykinin and sodium nitroprusside. Second, we studied 10 older (60 ± 2 years) healthy sedentary men before and after a 3 month aerobic exercise intervention. Net endothelial t-PA release was significantly blunted with age in the sedentary men. At the highest dose of bradykinin the increase in t-PA antigen release was ≈35 % less (   P < 0.05  ) in the older (from −1.0 ± 0.4 to 37.8 ± 3.8 ng (100 ml tissue)⁻¹ min⁻¹) compared with young (from 0.1 ± 0.6 to 56.6 ± 9.2 ng (100 ml tissue)⁻¹ min⁻¹) men. In contrast, the endurance-trained men did not demonstrate an age-related decline in the net release of t-PA antigen. After the exercise intervention, the capacity of the endothelium to release t-PA increased ≈55 % (   P < 0.05  ) to levels similar to those of the young adults and older endurance-trained men. Regulated endothelial t-PA release declines with age in sedentary men. Regular aerobic exercise may not only prevent, but could also reverse the age-related loss in endothelial fibrinolytic function.     

Antagonism of orexin receptor-1 in the retrotrapezoid nucleus inhibits the ventilatory response to hypercapnia predominantly in wakefulness

Recent data from transgenic mice suggest that orexin plays an important role in the ventilatory response to CO₂ during wakefulness. We hypothesized that orexin receptor-1 (OX₁R) in the retrotrapezoid nucleus (RTN) contributes to chemoreception. In unanaesthetized rats, we measured ventilation using a whole-body plethysmograph, together with EEG and EMG. We dialysed the vehicle and then SB-334867 (OX₁R antagonist) into the RTN to focally inhibit OX₁R and studied the effects of both treatments on breathing in air and in 7% CO₂. During wakefulness, SB-334867 caused a 30% reduction of the hyperventilation induced by 7% CO₂ (mean ± S.E.M., 135 ± 10 ml (100 g)⁻¹ min⁻¹) compared with vehicle (182 ± 10 ml (100 g)⁻¹ min⁻¹) ( P < 0.01). This effect was due to both decreased tidal volume and breathing frequency. There was a much smaller, though significant, effect in sleep (9% reduction). Neither basal ventilation nor oxygen consumption was affected. The number and duration of apnoeas were similar between control and treatment periods. No effect was observed in a separate group of animals who had the microdialysis probe misplaced (peri-RTN). We conclude that projections of orexin-containing neurons to the RTN contribute, via OX₁Rs in the region, to the hypercapnic chemoreflex control during wakefulness and to a lesser extent, non-rapid eye movement sleep.     

Inspiratory muscle training attenuates the human respiratory muscle metaboreflex

We hypothesized that inspiratory muscle training (IMT) would attenuate the sympathetically mediated heart rate (HR) and mean arterial pressure (MAP) increases normally observed during fatiguing inspiratory muscle work. An experimental group (Exp, n = 8) performed IMT 6 days per week for 5 weeks at 50% of maximal inspiratory pressure (MIP), while a control group (Sham, n = 8) performed IMT at 10% MIP. Pre- and post-training, subjects underwent a eucapnic resistive breathing task (RBT) (breathing frequency = 15 breaths min⁻¹, duty cycle = 0.70) while HR and MAP were continuously monitored. Following IMT, MIP increased significantly ( P < 0.05) in the Exp group (−125 ± 10 to −146 ± 12 cmH₂O; mean ± s.e.m. ) but not in the Sham group (−141 ± 11 to −148 ± 11 cmH₂O). Prior to IMT, the RBT resulted in significant increases in HR (Sham: 59 ± 2 to 83 ± 4 beats min⁻¹; Exp: 62 ± 3 to 83 ± 4 beats min⁻¹) and MAP (Sham: 88 ± 2 to 106 ± 3 mmHg; Exp: 84 ± 1 to 99 ± 3 mmHg) in both groups relative to rest. Following IMT, the Sham group observed similar HR and MAP responses to the RBT while the Exp group failed to increase HR and MAP to the same extent as before (HR: 59 ± 3 to 74 ± 2 beats min⁻¹; MAP: 84 ± 1 to 89 ± 2 mmHg). This attenuated cardiovascular response suggests a blunted sympatho-excitation to resistive inspiratory work. We attribute our findings to a reduced activity of chemosensitive afferents within the inspiratory muscles and may provide a mechanism for some of the whole-body exercise endurance improvements associated with IMT.     

Insulin hypersensitivity in mice lacking the V1b vasopressin receptor

We have reported that [Arg⁸]-vasopressin-stimulated insulin release is blunted in islet cells isolated from V1b receptor-deficient ( V1bR ^−/−) mice. In this study, we used V1bR ^−/− mice to examine the physiological role of the V1b receptor in regulating blood glucose levels in vivo , and we found that the fasting plasma glucose, insulin and glucagon levels were lower in V1bR ^−/− mice than in wild-type ( V1bR ^+/+) mice. Next, we evaluated glucose tolerance by performing an intraperitoneal glucose tolerance test (GTT). The plasma glucose and insulin levels during the GTT were lower in V1bR ^−/− mice than in V1bR ^+/+ mice. An insulin tolerance test (ITT) revealed that, after insulin administration, plasma glucose levels were lower in V1bR ^−/− mice than in V1bR ^+/+ mice. In addition, a hyperinsulinaemic–euglycaemic clamp study showed that the glucose infusion rate was increased in V1bR ^−/− mice, indicating that insulin sensitivity was enhanced at the in vivo level in V1bR ^−/− mice. Furthermore, we found that the V1b receptor was expressed in white adipose tissue and that insulin-stimulated phosphorylation of Akt as an important signaling molecule was increased in adipocytes isolated from V1bR ^−/− mice. Thus, the blockade of the V1b receptor could result, at least in part, in enhanced insulin sensitivity by altering insulin signalling in adipocytes.     

An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle

We tested the hypothesis that an acute decrease in muscle TCA cycle intermediates during contraction would compromise aerobic energy delivery. Male Wistar rats were anaesthetized and the gastrocnemius–plantaris–soleus (GPS) muscle complex from one leg was isolated and perfused with a red cell medium containing either saline (Con) or cycloserine (Cyclo; 0.05 mg g⁻¹), an inhibitor of alanine aminotransferase (AAT). After 1 h of perfusion, the GPS muscle was either snap frozen (Con-Rest, n = 11; Cyclo-Rest, n = 9) or stimulated to contract for 10 min (1 Hz, 0.3 ms, 2 V) with blood flow fixed at 30 ml min⁻¹ (100 g)⁻¹ and then snap frozen (Con-Stim, n = 10; Cyclo-Stim, n = 10). Maximal AAT activity was > 80% lower ( P < 0.001) in both Cyclo-treated groups (Rest: 0.61 ± 0.02; Stim: 0.63 ± 0.01 mmol (kg wet wt)⁻¹ min⁻¹; mean ± s.e.m. ) compared to Con (Rest: 3.56 ± 0.16; Stim: 3.92 ± 0.29). The sum of five measured TCAI (ΣTCAI) was reduced by 23% in Cyclo-Rest versus Con-Rest but this was not different ( P = 0.08). However, after 10 min of contraction, the ΣTCAI was 25% lower ( P = 0.006) in Cyclo-Stim compared to Con-Stim (1.88 ± 0.15 versus 2.48 ± 0.11 mmol (kg dry wt)⁻¹). Despite the acute decrease in TCAI after Cyclo treatment, the contraction-induced changes in markers of non-oxidative energy provision (phosphocreatine, ATP and lactate) and the decline in tension after 10 min of stimulation were similar compared to Con. These data do not support the hypothesis that the total muscle concentration of TCAI is causally linked to the rate of mitochondrial respiration during contraction.     

Rats exhibit aldosterone-dependent sodium appetite during 24 h hindlimb unloading

Hindlimb unloading (HU) is an animal model of microgravity and bed rest. In these studies, we examined the role of ingestive behaviours in regulating body fluid balance during 24 h HU. In the first experiment, all rats were given distilled water to drink while two groups were also given access to a sodium chloride solution (0.9% or 1.8%). Water and saline intakes were measured before, during and after 24 h of HU. Rats reduced water intake during 24 h HU in all conditions. During HU, rats increased their intakes of both saline solutions (0.9% NaCl ( n = 11): control 7.8 ± 3 ml; HU 18.2 ± 4 ml; recovery 8.9 ± 2.5 ml; 1.8% NaCl ( n = 7): control 1.0 ± 0.4 ml; HU 3.8 ± 0.3 ml; recovery 1.2 ± 0.5 ml). Although water intake decreased there was no reduction in total fluid intake when saline was available. Plasma volumes were reduced during HU compared to rats in a normal posture when only water was available to drink (control ( n = 11) versus HU ( n = 11): 4.0 ± 0.2 versus 3.4 ± 0.2 ml (100 g body weight)⁻¹). When 0.9% saline was available in addition to water, plasma volumes after 24 h HU were not different from rats in a normal posture (control ( n = 11) versus HU ( n = 12): 4.3 ± 0.4 versus 4.3 ± 0.1 ml (100 g body weight)⁻¹). Plasma aldosterone but not plasma renin activity was significantly elevated after 24 h HU. Central infusions of spironolactone blocked the increased intake of 1.8% saline that was associated with 24 h HU. Thus, HU results in an aldosterone-dependent sodium appetite and the ingestion of sodium may help maintain plasma volume.     

Increased glomerular angiotensin II binding in rats exposed to a maternal low protein diet in utero

In the rat, protein restriction during pregnancy increases offspring blood pressure by 20–30 mmHg. We have shown in an earlier study that this is associated with a reduction in nephron number and increased glomerular sensitivity to angiotensin II (Ang II) in vivo . Hence, we hypothesized that exposure to a maternal low-protein diet increases glomerular Ang II AT₁ receptor expression and decreases AT₂ receptor expression. To test this hypothesis, pregnant Wistar rats were fed isocalorific diets containing either 18% (control) or 9% (LP) protein from conception until birth. At 4 weeks of age, the kidneys of male offspring were harvested to measure cortical AT₁ and AT₂ receptor expression, ¹²⁵I-Ang II glomerular binding, tissue renin activity, tissue Ang II and plasma aldosterone concentrations. AT₁ receptor expression was increased (62%) and AT₂ expression was decreased (35%) in LP rats. Maximum ¹²⁵I-Ang II (¹²⁵I-Ang II) binding ( B _max) was increased in LP rats (control n = 9, 291.6 ± 27.4 versus LP n = 7, 445.7 ± 27.4 fmol (mg glomerular protein)⁻¹, P < 0.01), but affinity ( K _D) was not statistically different from controls (control 2.87 ± 0.85 versus LP 0.84 ± 0.20 pmol ¹²⁵I-Ang II, P = 0.059). Renal renin activity, tissue Ang II and plasma aldosterone concentrations did not differ between control and LP rats. Increased AT₁ receptor expression in LP rat kidneys is consistent with greater haemodynamic sensitivity to Ang II in vivo . This may result in an inappropriate reduction in glomerular filtration rate, salt and water retention, and an increase in blood pressure.     

Effects of insulin on adipose tissue blood flow in man

Adipose tissue blood flow (ATBF) rises after nutrient ingestion. It is not clear whether this is due to insulin. The aim of this study was to investigate the role of insulin in the regulation of subcutaneous ATBF. We have investigated the role of insulin in the regulation of ATBF in normal, healthy subjects in a three-step procedure to determine the functional level at which insulin may potentially exert its effect. Fifteen subjects were studied on two occasions. On the first visit, 75 g oral glucose was given. In the second, similar plasma concentrations of insulin and glucose were achieved by dynamic intravenous infusions of insulin and glucose. The increase in ATBF after oral glucose (4.2 ± 1.4 ml min⁻¹ (100 g tissue)⁻¹,   P = 0.01  ) was significantly greater (   P < 0.05  ) than that after intravenous infusions (1.5 ± 0.6 ml min⁻¹ (100 g tissue)⁻¹   P < 0.05  ). For the local delivery of potentially vasoactive substances and simultaneous measurement of ATBF, we describe a novel combination of methods, which we have called 'microinfusion'. We have used this technique to show that locally infused insulin, even at pharmacological concentrations, had no demonstrable effect on ATBF in nine subjects. We conclude that whilst insulin does not have a direct effect on ATBF, it is likely to be an important mediator, possibly acting via sympathetic activation. In the postprandial state, other candidate peptides and hormones are also likely to play important roles.     

Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise

The interleukin-6 (IL-6) output from subcutaneous, abdominal adipose tissue was studied in nine healthy subjects before, during and for 3 h after 1 h two-legged bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied in control experiments without exercise. The adipose tissue IL-6 output was measured by direct Fick technique. An artery and a subcutaneous vein on the anterior abdominal wall were catheterized. Adipose tissue blood flow was measured using the ¹³³Xe-washout method. In both studies there was a significant IL-6 output in the basal state and no significant change was observed during exercise. Post-exercise the IL-6 output began to increase after 30 min. Three hours post-exercise it was 58.6 ± 22.2 pg (100 g)⁻¹ min⁻¹. In the control experiments the IL-6 output also increased, but it only reached a level of 3.5 ± 0.8 pg (100 g)⁻¹ min⁻¹. The temporal profile of the post-exercise change in the IL-6 output closely resembles the changes in the outputs of glycerol and fatty acids, which we have described previously in the same adipose tissue depot. The difference is that it begins to increase ≈30 min before the glycerol and fatty acid outputs begin to increase. Thus, we suggest that the enhanced IL-6 production post-exercise in abdominal, subcutaneous adipose tissue may act locally via autocrine/paracrine mechanisms influencing lipolysis and fatty acid mobilization rate from this lipid depot.     

Neurovascular responses to mental stress

The effects of mental stress (MS) on muscle sympathetic nerve activity (MSNA) and limb blood flows have been studied independently in the arm and leg, but they have not been studied collectively. Furthermore, the cardiovascular implications of postmental stress responses have not been thoroughly addressed. The purpose of the current investigation was to comprehensively examine concurrent neural and vascular responses during and after mental stress in both limbs. In Study 1, MSNA, blood flow (plethysmography), mean arterial pressure (MAP) and heart rate (HR) were measured in both the arm and leg in 12 healthy subjects during and after MS (5 min of mental arithmetic). MS significantly increased MAP (Δ15 ± 3 mmHg; P < 0.01) and HR (Δ19 ± 3 beats min⁻¹; P < 0.01), but did not change MSNA in the arm (14 ± 3 to 16 ± 3 bursts min⁻¹; n = 6) or leg (14 ± 2 to 15 ± 2 bursts min⁻¹; n = 8). MS decreased forearm vascular resistance (FVR) by −27 ± 7% ( P < 0.01; n = 8), while calf vascular resistance (CVR) did not change (−6 ± 5%; n = 11). FVR returned to baseline during recovery, whereas MSNA significantly increased in the arm (21 ± 3 bursts min⁻¹; P < 0.01) and leg (19 ± 3 bursts min⁻¹; P < 0.03). In Study 2, forearm and calf blood flows were measured in an additional 10 subjects using Doppler ultrasound. MS decreased FVR (−27 ± 10%; P < 0.02), but did not change CVR (5 ± 14%) as in Study 1. These findings demonstrate differential vascular control of the arm and leg during MS that is not associated with muscle sympathetic outflow. Additionally, the robust increase in MSNA during recovery may have acute and chronic cardiovascular implications.     

An association between cutaneous sensitivity to histamine and HLA phenotype

Four hundred and twenty randomly chosen subjects from a normal population were HLA typed and tested for cutaneous sensitivity to histamine by prick testing with 5 concentrations of histamine (10⁻³, 10⁻², 10⁻¹, 1, 10 mg ± ml⁻¹). Positive responses to 10⁻¹ mg ± ml⁻¹ histamine occurred in 41% of the subjects, and particularly those with HLA-B7 (55%) (p < 0.005). It is concluded that genes within the major histocomptability complex influence cutaneous responses to histamine.     

CNS-induced natriuresis, neurohypophyseal peptides and renal dopamine and noradrenaline excretion in prehypertensive salt-sensitive Dahl rats

To identify defects in the salt-sensitive Dahl rat (Dahl-S), the natriuretic, catecholaminergic and pressor responses to 60-min elevation of the cerebroventricular sodium concentration (CNS-induced natriuresis) were compared between prehypertensive salt-sensitive Dahl-S and salt-resistant Dahl rats (Dahl-R). The plasma concentrations of the rat natriuretic hormone oxytocin, which has implications for the development of hypertension, and vasopressin (AVP) were also measured. Basal sodium and catecholamine excretion and mean arterial blood pressure (MAP) were similar in both strains. Sodium excretion during CNS stimulation increased more than 15-fold in Dahl-R but only 10-fold in Dahl-S. Dopamine excretion increased only transiently and similarly in both strains. Noradrenaline excretion and response to CNS stimulation were similar, suggesting a comparable sympathetic nervous activity between the strains. MAP increased comparably in Dahl-R and Dahl-S. Plasma AVP concentration was similar in both strains while plasma oxytocin concentration after CNS stimulation was more than 2-fold higher in Dahl-S than in Dahl-R. In conclusion, the prehypertensive Dahl-S has an attenuated natriuretic response to elevations of the cerebroventricular fluid sodium concentration and a higher plasma level of the natriuretic hormone oxytocin. Dopamine is not a mediator of CNS-induced natriuresis in neither strain. The attenuated natriuretic response may partly explain the salt-sensitivity in Dahl-S, and the higher plasma oxytocin value may either represent an effort to compensate for the deficient natriuretic response or reflect a primary defect in this system. Due to the known involvement of oxytocin in central MAP regulation in some hypertensive animal models, the findings warrant further investigation.