Compliance of the interstitial space in rats

The contribution to the extracellular fluid volume (ECV) from plasma volume (PV) and the total interstitial volumes contained in skin (IFVS) and skeletal muscle (IFVM) has been studied in rats over a wide range of overhydration and dehydration. ECV was measured as the two-hour distribution space for ⁵¹Cr-EDTA after nephrectomy while PV was measured with radiolabelled albumin or erythrocytes. Total interstitial volumes in skin and skeletal muscle were calculated from measurement of local interstitial volumes and the amount of skin and skeletal muscle in the rat. In control conditions ECV was on average 24.12 ml/100 g body weight. PV was 11.0% of ECV in control while IFVS and IFVM was 28.1% and 19.0% respectively. In dehydration the change in PV was 13.3% of the change in ECV, while the change in IFVS and IFVM was 30.0% and 21.0% of the change in ECV respectively. In overhydration (ECV on average 33.76 ml/100 g rat) the changes in PV, IFVS and IFVM were 7.5%, 22.1% and 17.2% of the change in ECV respectively. The regression coefficients describing the change between ECV and IFVS and IFVM were not significantly different in overhydration and dehydration while the regression coefficient between ECV and PV in overhydration was significantly less than the regression coefficient in dehydration. Thus, the fraction of ECV contained in skin and skeletal muscle is similar over the range of hydration studied. The fraction of ECV located in plasma is similar in control and dehydration, while in overhydration less of ECV is localized in plasma. The observed distribution of ECV validates previous compliance measurements based on pressure measurements in skin together with measurements of total ECV. The present results support the hypothesis that regulation of the total extracellular volume can be accomplished through regulation of plasma volume alone without the need for volume receptors located in the interstitium.     

Compliance of the interstitial space in rats I. Studies on hindlimb skeletal muscle

Interstitial compliance, defined as the ratio between changes in interstitial fluid volume (ΔIFV) and interstitial fluid pressure (ΔIFP), was determined for rat skeletal muscle. IFV was measured as the extravascular distribution space for ⁵¹Cr-EDTA, while sharpened micropipettes connected to a servo-controlled counterpressure system were used to measure IFP. The experimental protocol was designed to bring about acute (2–4 h) and chronic (24–28h) tissue over- and dehydration. During dehydration, the average compliance was 0.056 ml/g dry weight · mmHg, corresponding to 1.40 ml/100 g wet tissue mmHg, and was not significantly different in acute and chronic experiments. In hydration (acute and chronic), compliance increased several-fold when IFV increased. Even at greatly increased IFV, IFP did not rise more than 1 to 1.5 mmHg above control level. Since control IFV amounts to 10 ml/100 g wet tissue, IFV will decrease by 14% when IFP falls by 1 mmHg from this control level. Provided unchanged interstitial protein mass the dehydration will cause interstitial fluid colloid osmotic pressure to increase by somewhat more than 1 mmHg—from a control level of 9 mmHg. Furthermore, since IFP was not increased by more than 1 to 1.5 mmHg during hydration, an increase in IFP plays a minor role in edema-prevention compared to dilution and/or washout of interstitial proteins.     

The relationship between interstitial fluid pressure and volume in rat trachea

A change of interstitial fluid volume (IFV) will normally change the interstitial fluid pressure (P_if) so as to counteract further fluid movement across the capillaries and changes in IFV. Contrary to this, several acute inflammatory reactions in the trachea are associated with increased negativity of P_if, which will interstitial fluid balance in the trachea, interstitial compliance (ΔIFV/ΔP_if) was measured in pentobarbital anaesthetized rats. IFV was measured as the plasma equivalent extravascular distribution space of [⁵¹Cr]EDTA. P_if was measured in the same animal with sharpened glass pipettes (diameter 3–6 μm) connected to a servocontrolled counterpressure system. In dehydration (30 mL saline i.v., n=10) interstitial compliance was 0.083 mL g dry wt^-1 mmHg^-1. Since control IFV was 1.046 mL g dry wt^-1 (n=10) the interstitial compliance is 8% of IFV per mmHg. In overhydration (30 mL NaCl, n=10) and dextran anaphylaxis (1 mL dextran 70, n=10) compliance remained the same for the first 15% increase in IFV and then increased several-fold since P_if did not increase more than 2 mmHg above control level. The increased negativity of P_if by -10 mmHg associated with acute inflammation will require a reduction of IFV by 80% when interstitial compliance is 8% per mmHg. A more likely explanation is therefore that structural rearrangements are responsible for the events leading to increased negativity of P_if in acute inflammation.     

Interstitial fluid volume,colloid osmotic and hydrostatic pressures in rat skeletal muscle. Effect of venous stasis and muscle activity

The effect of 24 h caval/iliac venous obstruction on interstital fluid volume (IFV), hydrostatic (P|) and colloid osmotic (COP₁) pressure in hindlimb skeletal muscle was studied in three groups of rats: Group I (GI), Intact innervation, unrestricted motor activity. Group II (GII), Sympathectomized, unrestricted. Group III (GIII), Motoric and sympathetic denervation + immobilization of the hindlimbs. Subcutaneous edema was present in all groups at femoral venous pressure (P_v) exceeding 13 mmHg. Skeletal muscle edema was seen in G III at P_v above 12 mmHg, in two rats in G II at P_v of 18 and 23 mmHg, but in no rats in G I. Whithout venous obstruction, control COP₁ was 8–10 mmHg in all groups. With increasing P_v, COP fell moderately in GI and GII: ΔCOP₁/AP_v= 0.22. In GIII, COP, fell from a control of 8.2 to 3.5 mmHg at a P_v of 12 mmHg (ACOP₁/AP_v=0.52), but remained constant with further rise in P_v P₁ was about 0 mmHg in controls and 1–2 mmHg in rats with muscle edema. IFV rose by 6% per mmHg increase in P_v in G III, and 2% in G I and G II. This expansion of IFV may explain about 70% of the fall in COP₁, the remaining being due to lymphatic washout of interstitial proteins. It is concluded that normal muscle activity together with dilution and washout of interstitial proteins constitute the main edema preventing mechansms in skeletal muscle.     

Measurement of interstitial fluid pressure: Comparison of methods

Interstitial fluid pressure (IFP), i.e., the pressure in a saline-filled tube brought into contact with the interstitium, has been measured in cats with two “acute” [micropipettes and wick-in-needle (WIN)] and two chronic (perforated and porous capsules) methods. In a control situation, similar pressures of −1.5 and −1.6 mm Hg were recorded in skin with micropipettes and both types of capsules, respectively, while WIN pressure in subcutis was −1.2 mm Hg. IFP in skeletal muscle was −0.5, −0.5, and −1.1 mm Hg as recorded with micropipettes, WIN, and porous capsules, respectively. During infusion of Ringer's solution, pressures in both types of capsules rose by 4 to 6 mm Hg, while pressure recorded with the acute methods increased by 1 to 1.5 mm Hg only. Two hours after infusion all techniques gave similar pressures. Peritoneal dialysis for 2 hours reduced micropipette and WIN pressures by 3 to 4 mm Hg. Pressure in perforated capsules fell by 10 mm Hg during dialysis and remained low for an additional 2 hours, while porous capsule pressure fell by 7 mm Hg during dialysis but thereafter increased and reached the pressure recorded with micropipettes and WIN 2 hours after ended dialysis. In both overhydration and dehydration, capsules probably react to changes in interstitial fluid colloid osmotic pressure; in overhydration the capsules react also to changes in capillary pressure, resulting in the discrepancy between chronic and acute methods during non-steady-state conditions. In conclusion, acute and chronic methods record similar pressures during steady-state conditions, but the chronic methods are sensitive to changes in vascular pressure and interstitial fluid colloid osmotic pressure and are therefore not suitable for measuring the changes that occur in IFP within a few hours.     

Transcapillary albumin extravasation in rat skin and skeletal muscle: effect of increased venous pressure

Plasma-to-tissue transport of radioactively labelled albumin has been used to study the effect of increased venous pressure on transcapillary albumin transport. Venous pressure was increased by inflating a balloon catheter in the inferior caval vein. Plasma-to-tissue transport of albumin was taken as the extravascular distribution space (EValb) for 125I-labelled human serum albumin (I-HSA) after 1 h. Venous pressure was increased from 2 to 20 mmHg in the experimental group. Interstitial fluid volume (IFV) was measured as the extravascular distribution space for 51Cr-EDTA. In control EValb was 9.24 X 10(-3) ml g-1 d. wt (SD = 1.28, n = 8) and 3.67 X 10(-3) ml g-1 d.wt (SD = 0.94, n = 8) in skin and skeletal muscle, respectively. Increasing venous pressure raised EValb and IFV in skin and skeletal muscle, but the increase in EValb was about 3 and 5% of the rise in IFV, resulting in capillary reflection coefficients for albumin of 0.94 in skin and 0.98 in skeletal muscle. The low transcapillary albumin transport relative to water transport is compatible with a two-pore model of transcapillary exchange where large pores (250 A) accounts for less than 5.5 and 2.5% of the total capillary filtrate of fluid in skin and skeletal muscle, respectively.     

Arterial blood pressure and general sympathetic activation in essential hypertension during stimulation

We asked whether exaggerated blood pressure (BP) reactivity in patients with essential hypertension (HT) is a sign of specific activation of the cardiovascular system or of generalized sympathetic activation. Fourteen patients with essential hypertension and 14 matched normotensive (NT) controls were subjected to tasks involving attentional demands, mental arithmetic, a cold pressor test and isometric muscular contraction. Systolic and diastolic BPs, skin and muscle blood flows, heart rate, skin conductance level and fluctuations during each task were recorded. Urine samples for determination of epinephrine and norepinephrine excretion were collected after task completion. All tasks caused BP increases in both groups. HT showed greater absolute and percentage BP reactivity than NT during isometric muscle contraction. Variables for which reactivity differences were observed were poorly correlated across tasks both in HT and NT, whereas resting values prior to each task were highly correlated in both groups. Skin conductance activity, epinephrine and norepinephrine excretion rates being examples of non-cardiovascular sympathetic nervous system (SNS) indicators did not separate HT from NT. Thus, the exaggerated pressor response in HT is not accompanied by signs of generalized SNS activation.     

Pressure-volume relationship for rat dermis: compression studies

The relationship between tissue hydrostatic pressure and fluid content is an important determinant of the response of the microvascular exchange system to perturbations. However, only a limited number of studies relating these parameters have been reported. To add to this body of information, fully swollen rat dermis in vitro was subjected to successive compressive loads in an apparatus in which tissue thickness changes were monitored. At steady-state the mechanical load on the tissue was balanced by the interstitial fluid pressure within the tissue while the fluid content of the tissue was determined from the unstressed tissue fluid content and changes in tissue thickness. The range of conditions investigated was from moderate overhydration through normal tissue fluid content to significant dehydration. From the relationship between interstitial fluid pressure and tissue fluid content (expressed as mass of fluid per mass of fat-free dry tissue) the tissue compliance was determined. Compliance, defined as the rate of change of the tissue fluid content with changes in interstitial pressure, increased with tissue hydration. The compliance determined using compressive loads and steady-state response of tissue thickness compares favourably with the limited amount of information available about this tissue property which is critical in the determination of tissue fluid balance. Compliance ranged over one order of magnitude for the conditions studied and at normal hydration, tissue fluid volume changed by about 6.6% per mmHg in tissue hydrostatic pressure.     

Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats

Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P < 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.     

Sprint-interval training-induced alterations of Myosin heavy chain isoforms and enzyme activities in rat diaphragm: effect of normobaric hypoxia

The purpose of this study was twofold: (i) to investigate if sprint-interval training (SIT) alters myosin heavy chain (MyHC) isoform composition and bioenergetic properties within the rat diaphragm, and (ii) to determine if mild normobaric hypoxia would enhance the effects of SIT-induced diaphragmatic adaptation. Male Wistar rats (8 weeks old) were randomly assigned to one of four groups (n = 7/group): (i) normoxic control (NC); (ii) normoxic training (NT); (iii) hypoxic control (HC); or (iv) hypoxic training (HT). The NT and HT groups were engaged in SIT (1 min sprint and 2-5 min rest, 6-10 sets/day, 5-6 days/week) on a treadmill for 9 weeks. Animals in the HC and HT groups were exposed to normobaric hypoxia (14.5% O(2)) during an SIT program from the 4th week of the training period. After completion of the training program, MyHC composition, citrate synthase (CS) activity, and lactate dehydrogenase (LDH) activity in the diaphragm and plantaris muscle were analyzed. An analysis of diaphragmatic MyHC composition demonstrated increased type IIa and decreased type IId/x for both training groups (P < 0.05), with the HT group producing greater changes than the NT group (P < 0.05). The plantaris muscle, however, showed increased Type IIa and IId/x and decreased Type IIb for both the NT and HT groups (P < 0.05). CS activity increased only for the training groups (P < 0.05), and this change was greater for the HT group in the diaphragm and for the NT group in the plantaris muscle (P < 0.05). Further, diaphragmatic LDH activity in HT was significantly lower (P < 0.05) than in HC and NT. These findings demonstrated that SIT could induce alterations in MyHC composition from fast to slow within type II isoforms and also improve the oxidative capacity in the diaphragm and plantaris muscles. It is of importance that our data revealed that SIT-induced diaphragmatic adaptations were enhanced when SIT was performed in normobaric hypoxia.     

高血压患者血管紧张素转换酶基因多态性分析

目的探讨血管紧张素转换酶基因多态性与北京房山地区高血压遗传易感相关性。方法应用聚合酶链反应（PCR）技术,检测287例高血压患者和316例正常血压对照者的ACE基因多态性。结果群体相关分析结果表明,高血压组（包括原发性高血压和合并空腹血糖升高的高血压患者）ACE基因的D等位基因及其纯合基因型（D／D）频率较正常血压对照组明显升高（x2＝4．14,P＜0．05）。原发性高血压患者组ACE基因缺失纯合基因型频率较高血压伴有空腹血糖升高组显著增加,其频率分别为30.8％和19．2％（x2＝4．45,P＜0．05）,而高血压伴空腹血糖升高者与对照者间D／D纯合基因型频率无显著差异。结论ACE基因插入／缺失多态性可能与房山地区汉族原发性高血压相关联。     

Cell Proliferation of Cultured Human Cancer Cells are Affected by the Elevated Tumor Pressures that Exist In Vivo

Elevated interstitial fluid pressure (IFP) is observed in most solid tumors. However, the study of the cellular processes of tumors and the development of chemotherapy are routinely studied using in vitro culture systems at atmospheric pressure. Using a new pressurized cell culture system, we investigated the influence of hydrostatic pressure on population dynamics of three primary osteosarcoma (HOS, U2OS, SaOS2) and two metastatic tumor cell lines (MCF7 breast, H1299 lung) that invade bone. Values of IFP in normal human bone and muscle, and in osteosarcoma tumors obtained during their surgical biopsy established the hydrostatic pressure range for the in vitro cell studies. The IFP values were obtained from a retrospective review of patient records. IFP from confirmed osteosarcoma was 35.9± 16.2 mmHg. Tumor IFP was significantly higher than muscle IFP (p < 0.001) and bone IFP (p < 0.003).The in vitro study measured the cell-line proliferation using hydrostatic pressures of 0, 20, 50 and 100 mmHg. The findings suggest that hydrostatic pressure either increases or decreases tumor proliferation rates depending on cell type. Furthermore, cell death was not associated with apoptosis.     

Human body-fluid distribution during exercise in hot,temperate and cool environments

Using a simultaneous-dilution technique, we investigated body-fluid volume changes during exercise in seven males, during 50 min of cycling (50% maximal work rate) in hot (36.2 °C), temperate (22.0 °C) and cool conditions (14.4 °C). Total body water (TBW), extracellular fluid (ECFV), plasma (PV) and erythrocyte volumes (RCV) were measured, while blood volume (BV), interstitial fluid volume (IFV), extracellular water (ECW) and intracellular water volumes (ICW) were derived. During the initial 10 min of cycling, BV decreased in all environments (P = 0.01), primarily because of a PV reduction (P = 0.01), while IFV, ECFV and ICW were not significantly changed. By 30 min, BV recovered in the temperate and cool conditions, despite mass losses of 563 and 520 mL (respectively), but remained depleted in the hot condition (P = 0.01). The 50-min volume changes revealed that, throughout exercise, body-fluid losses appeared to be drawn primarily from the extracellular space, regardless of air temperature. In the hot condition, the PV change represented 63% of the TBW loss, with the ICW contributing 23%. It was concluded that, during cycling, progressive dehydration mainly affected the extracellular space, with the intravascular and intracellular spaces being defended in less stressful conditions.     

Interstitial adenosine concentration in rat red or white skeletal muscle during systemic hypoxia or contractions

Interstitial adenosine concentrations in red soleus (SL) or white extensor digitorum longus (EDL) muscles of anaesthetised rats were determined using microdialysis and HPLC. Systemic hypoxia was induced by ventilating the animals with 10% oxygen in nitrogen for 15 min: arterial PO2 decreased from 111.8 +/- 10.9 to 42.2 +/- 4.3 mmHg (n = 4; P < 0.01) and mean systemic arterial blood pressure from 97.6 +/- 4.9 to 59.0 +/- 3.6 mmHg (n = 22; P < 0.001). The interstitial adenosine concentration was not significantly changed from its control values of 294 +/- 44 nM (n = 20) in EDL and 302 +/- 36 nM (n = 20) in SL during hypoxia or the recovery period. The interstitial lactate concentration did not change in the early part of the hypoxia but increased from 1.0 +/- 0.2 to 1.4 +/- 0.3 mM (n = 6; P < 0.05) in SL and from 2.0 +/- 0.4 to 2.4 +/- 0.4 mM (n = 6; P < 0.05) in EDL during the later part of the hypoxia, and remained elevated in the recovery period. Muscle contractions (2 Hz for 15 min) produced a transient increase in the interstitial adenosine concentration of SL from 150 +/- 35 to 244 +/- 75 nM (n = 10; P < 0.05) during the first 5 min of stimulation. In EDL the interstitial adenosine concentration increased from 145 +/- 50 to 435 +/- 144 nM (n = 10; P < 0.05) in the later part of the contraction and remained elevated in the early part of the recovery period. These data suggest that: (i) in systemic hypoxia adenosine does not appear in the interstitial space, which rules out its release from skeletal muscle, although it may be formed by the vascular tissues in this condition; (ii) adenosine is formed in the interstitial space of skeletal muscle during muscle contractions; (iii) there is slow clearance of adenosine from the interstitial space of white muscle, perhaps due to the low vascularity of the tissue.     

Role of glomerular epithelial cell injury in the pathogenesis of glomerular scarring in the rat remnant kidney model.

We investigated the roles of glomerular epithelial cell (GEC) pathology and dysfunction in the pathogenesis of glomerular scarring and attempted to separate them from direct hypertensive injury in the 5/6 nephrectomy (RK) model of glomerular injury. Male WKY rats weighing 200 g were studied 6 weeks after RK, when approximately one-half had developed systemic hypertension (systolic blood pressure > or = 150 mm Hg) (HT), and one-half were normotensive (NT). The incidence of glomerular necrosis and scarring was greatest in the HT rats (P = 0.0259), and vascular necrosis was only seen in 4 of 11 HT rats. The RK group had increased glomerular diameters (HT, 174 mu mean; NT, 171 mu; sham, 142 mu; P = 0.0014 by analysis of variance). There was foot process effacement in the HT and NT groups (HT, 104 filtration slits/100 mu glomerular basement membrane; NT, 112 mu; sham, 143 mu; P < 0.005 by analysis of variance), but GEC separation from the glomerular basement membrane was not significant in either HT or NT rats. GEC function was determined from protamine-heparin aggregate disappearance curves, and the curves, representing GEC endocytosis, were not different in either HT or NT groups compared with the sham-operated groups. These findings suggest that GEC function is preserved in RK, and the changes in glomerular size and GEC morphology are nonlethal and adaptive. The morphological appearance of the acute glomerular and vascular lesions and their presence only in HT animals is consistent with a hypertensive pathogenesis. The glomerular sclerosis seen in both HT and NT may result from either resolution of acute lesions with scarring and/or adaptive changes in glomerular structure and cellular functions other than the GEC clearance function we studied.     

Exercise but not Prostanoids Enhance Levels of Vascular Endothelial Growth Factor and other Proliferative Agents in Human Skeletal Muscle Interstitium

In the present study we examined whether exercise and prostanoids have an effect on the muscle interstitial concentration of vascular endothelial growth factor (VEGF) and on the proliferative effect of muscle interstitial fluid. Dialysate from resting and exercising human skeletal muscle, obtained either during control conditions or during cyclooxygenase inhibition, was examined for its content of VEGF and for its effect on endothelial cell proliferation. Microdialysis probes with high (960 kDa) and low (5 kDa) molecular-mass cut-off membranes were placed in the vastus lateralis muscle of healthy young males. The subjects performed one-legged knee extensions (20 W). The concentration of VEGF in the 960 kDa dialysate was greater (   P < 0.05  ) during exercise compared to at rest (67 ± 28 vs. 230 ± 22 pg ml⁻¹). The rate of endothelial cell proliferation was 2.7-fold higher (   P < 0.05  ) with the 960 kDa dialysate from resting muscle than with perfusate and was 5.8-fold higher (   P < 0.05  ) than the perfusate value with dialysate from exercising muscle. VEGF was not enhanced with exercise in the 5 kDa dialysate, yet the exercise dialysate induced a 1.9-fold higher (   P < 0.05  ) proliferation than the resting dialysate. Cyclooxygenase inhibition did not affect the VEGF concentration or the proliferating effect of the dialysates (   P > 0.05  ). This study demonstrates for the first time that VEGF is present in the interstitium of human skeletal muscle and that exercise enhances the interstitial concentration of VEGF and of other, as yet unidentified, angiogenic compounds. Products of cyclooxygenase do not appear to have an effect on the release of VEGF or other proliferative agents in human skeletal muscle.     

Role of vascular bed compliance in vasomotor control in human skeletal muscle

The current view of neurogenic vasomotor control in skeletal muscle is based largely on changes in vascular bed resistance. The purpose of this study was to determine to what extent vascular bed compliance may also play a role in this regulation. For this purpose, pressure waveforms (Millar and Finometer) and flow waveforms (Doppler ultrasound) were measured simultaneously in the brachial artery of seven healthy individuals during physiological manoeuvres which were expected to produce non-neurogenic changes in resistance (wrist-cuff occlusion; n = 5) or compliance (arm elevation; n = 6) of the forearm vascular bed. Vascular resistance (R) was calculated from the average flow and pressure values. A lumped Windkessel model was used to obtain vascular bed compliance (C) from these concurrently measured waveforms. Compared with baseline (3.81 +/- 1.59 ml min(-1) mmHg(-1)), wrist occlusion increased R (65 +/- 75%; P < 0.05) with minimal change in C (-15 +/- 16%; n.s.). Compared with the arm in neutral position (0.0075 +/- 0.003 ml mmHg(-1)), elevation of the arm above heart level produced a 86 +/- 41% increase in C (P < 0.05) with little change in R (-5 +/- 11%). In addition, neurogenic changes were assessed during lower body negative pressure (LBNP) and a cold pressor test (CPT; n = 7). Lower body negative pressure induced a 29 +/- 24% increase in R and a 26 +/- 12% decrease in C (both P < 0.05). The CPT induced no consistent change in R but a 22 +/- 7% reduction in C (P < 0.05). It was concluded that vascular bed compliance is an independent variable which should be considered along with vascular bed resistance in the mechanics of vasomotor regulation in skeletal muscle.     

Autonomic Nervous System Function and Essential Hypertension: Individual Response Specificity With and Without Beta-Adrenergic Blockade

The aim of the present research was to study individual response specificity in 22 male patients having essential hypertension (HT) and to compare these patients with age-matched male normotensive controls (NT). Four stimuli, letter identification, mental arithmetic, cold pressor and isometric exercise, were administered while recordings were made of: systolic and diastolic blood pressures, heart rate, respiration, forearm and hand blood flows, and skin conductance level and fluctuations. After each session urine samples were collected and epinephrine and norepinephrine levels were analyzed. Twelve subjects in the HT group were given beta-adrenergic blocking agents and retested 1 to 21 months (X?= 12 months) after the first session. Each response was standardized, using NT as the reference group. Intraclass correlations were computed to evaluate whether HT males reacted with a more consistent hierarchy of responses than did NT. Intraclass correlations were significantly higher among the patients than in the control group, regardless of whether the blood pressure response was included or excluded in the computation of the intraclass correlations. Thus, we conclude that male HT patients show more individual response specificity than NT controls. Beta-adrenergic receptor antagonists reduced levels of cardiovascular activity and attenuated reactivity but did not affect amount of specificity. Thus, intraclass correlations provide unique and useful information, since they are not related to blood pressure reactivity or to urinary catecholamine levels, nor affected by beta-adrenergic blockade.     

Quantification and localisation of damage in rat muscles after controlled loading; a new approach to study the aetiology of pressure sores.

To obtain more insight in the aetiology of deep pressure sores, an animal model was developed to relate controlled external loading to local muscle damage. The tibialis anterior muscle (TA) and overlying skin of a rat were compressed between indentor and tibia. Loads of 10, 70 and 250kPa at skin surface were applied for 2 or 6h. During half of the 10 and 250kPa experiments interstitial fluid pressure (IFP) in the TA was measured. The TAs were excised 24h after load application. Both amount and location of damage were assessed by histological examination using a semi-automated image-processing program. In six of eleven loaded muscles damage was found. The damage was located from superficial to deep muscle tissue in a zone never exceeding the diameter of the indentor. The IFP measurements interfered with the occurrence of damage; application of 10 and 70kPa loads only caused damage when combined with IFP measurements, whereas IFP measurements increased damage at 250kPa loads. The results showed that the developed animal model can be used to provoke local damage by applying a controlled load and that the amount and location of damage can be assessed using the newly developed techniques.     

Blood pressure maintenance in awake dehydrated rats: renin, vasopressin, and sympathetic activity

The role of vasopressin, the renin system, and sympathetic activity in sustaining blood pressure in the dehydrated state was investigated in normotensive nonanesthetized male Wistar rats. After 48-h dehydration, plasma arginine vasopressin was 14.0 +/- 1.7 pg/ml and plasma norepinephrine 0.46 +/- 0.05 ng/ml. In another group of rats in which the angiotensin converting enzyme inhibitor (MK 421, 5 mg po twice daily) was administered throughout the dehydration period, blood pressure was reduced by more than 20% (P less than 0.001), and both plasma arginine vasopressin and norepinephrine were higher at 23.4 +/- 3.9 pg/ml (P less than 0.01) and 0.83 +/- 0.07 ng/ml (P less than 0.01), respectively. Taken together, in rats with or without converting enzyme blockade, there was an inverse correlation between mean blood pressure and plasma arginine vasopressin (r = 0.67, P less than 0.01) as well as plasma norepinephrine (r = 0.82, P less than 0.01) levels. The acute administration of a specific vasopressin pressor inhibitor (dPVDAVP) reduced mean blood pressure in the rats with a blocked renin system by 16.9 mmHg (P less than 0.001). In rats without converting enzyme inhibition, the induced fall was only 6.4 mmHg. These results indicate that following 48-h dehydration the renin angiotensin system interacts with the vasopressin secretory mechanism to sustain blood pressure, with renin playing a predominant role. They further suggest that, following blockade of the renin system, activation of the sympathetic nervous system probably also contributes to blood pressure maintenance.