Cerebrospinal fluid pressure of anaesthetized rats during intracerebroventricular infusion

Increases in cerebrospinal fluid pressure (CSFP) were measured in the lateral ventricle in barbiturate anaesthetized male Sprague Dawley rats during intracerebroventricular (IVT) infusions into the contralateral ventricle. IVT infusions of isotonic artificial CSF (art-CSF) solutions at 10 and 38 microliters/hr increased mean CSFP from control preinfusion level of 3.6 cm H2O to 4.6 cm H20 (n.s.) and 5.2 cm H2O (p less than 0.01) respectively with CSFP appearing to attain equilibrium after 30-60 min of infusion. IVT infusion of hyperosmolar art CSF solutions (saccharide and salt solutions of approximate 1000 mOsm/kg) at 38 microliters/hr resulted in a larger increase of CSFP which equilibrated at 8.5 cm H2O (p less than 0.001) after 90 min of infusion. It is suggested that on the basis of CSFP measurements in these and other experiments cited that IVT infusions be run at infusion rates of less than 40 microliters/hr to ensure minimal physiological change.     

Interstitial compliance and transcapillary fluid balance in renal hypertensive rats

Local interstitial fluid volume (IFV) and pressure (IFP) were used to estimate interstitial compliance (= delta IFV/delta IFP) in skin and skeletal muscle of normotensive (NT) and renal hypertensive rats (HT). The IFV was measured as the extravascular 51Cr-EDTA space, and IFP with micropipettes (tip diameter 2-4 microns) connected to a servocontrolled counter-pressure system. After control measurements, overhydration was induced by infusion of saline, 10% of body weight i.v. with or without venous stasis. Alternatively, dehydration was induced by peritoneal dialysis with 20% glucose or by furosemide infusion with or without 24 h fluid deprivation. Control ECV averaged 24.94 and 24.73 ml per 100 g in NT and HT, respectively (P greater than 0.05). Control PV averaged 2.81 and 3.28 ml per 100 g in NT and HT, respectively (P = 0.061), and control IFP was more positive in HT than in NT: 0.4 mmHg in skin (P less than 0.05) and 0.2 mmHg in skeletal muscle (P greater than 0.05). Dehydration changed PV significantly more in HT than in NT (P less than 0.05). The interstitial volume-pressure curve was linear in dehydration and the initial part of overhydration but gradually levelled off, and the maximal rise in IFP was 1-1.5 mmHg in skin and muscle. Interstitial compliance was calculated from the dehydration part of the volume-pressure curve and was in NT 14% per mmHg both in skin and skeletal muscle. In HT, compliance during dehydration was 10.2 and 20.7% reduction in IFV per mmHg fall in IFP in skin and muscle, respectively, not significantly different from corresponding values in NT (P greater than 0.05). We conclude that HT had unaltered ECV and a tendency to higher PV, and that interstitial compliance was not significantly different in normotensive and hypertensive rats.     

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.     

Autoregulation of renal blood flow in the rat: effects of growth and uninephrectomy

As a result of normal maturation or after reduction in renal mass, renal blood flow (RBF) progressively increases. However, the effects of renal growth on the relationship of RBF to renal perfusion pressure (RPP) have not been systematically investigated. We examined RBF as a function of RPP in anesthetized young and adult rats that had been subjected to uninephrectomy or sham operation 3-4 wk previously. As a result of normal growth, mean arterial blood pressure increased from 94.1 +/- 2.7 (SE) to 118.9 +/- 4.2 mmHg. The calculated autoregulation factor, in which a value less than 1 indicates the presence of autoregulation, was 0.44 +/- 0.10 over RPP 70-100 mmHg and 1.74 +/- 0.25 over RPP 40-70 mmHg in sham-operated young animals. In adult sham-operated rats, the factor was 0.38 +/- 0.07 over RPP 100-130 mmHg and 1.03 +/- 0.07 over RPP 70-100 mmHg. Uninephrectomy in adults resulted in a 30% rise in RBF over RPP 100-130 mmHg, and there was no change in the autoregulation factor. Uninephrectomy in young rats, however, resulted in a 35% rise in RBF at RPP = 100 mmHg with only a 17% rise at RPP = 70 mmHg, and the autoregulation factor increased to 0.91 +/- 0.10 over this range of RPP. We conclude that the autoregulatory range shifts with increasing blood pressure during normal growth and that autoregulation is "reset" to higher RBF in the uninephrectomized adult rat. Although autoregulation takes place in the young animal, uninephrectomy alters the relationship of RBF to RPP such that autoregulation is impaired.     

Effects of hypotension induced by adenosine on brain surface oxygen pressure and cortical cerebral blood flow in the pig

Six pigs were anaesthetized with ketamine in combination with fentanyl and droperidol and paralysed with pancuronium. The pigs were tracheotomized and ventilated mechanically. Mean arterial blood pressure, MABP, was lowered from 97 +/- 21 mmHg stepwise to 58 +/- 2, 33 +/- 4 and 22 +/- 4 mmHg by intravenous infusion of adenosine (4-8 mg kg-1 min-1). Regional cerebral blood flow (rCBF) was measured directly onto the cortex of the brain by local atraumatic application of 133xenon. Brain surface oxygen pressure (PtO2) was obtained using a multiwire oxygen surface electrode. At the level of 60 mmHg, rCBF showed a significant increase, while flow values were not changed from initial values with further hypotension. Ten minutes after adenosine was discontinued, rCBF showed a rebound effect with higher values than initially. During normotension mean cortical PtO2 varied between 2.1 KPa and 3.9 kPa. During adenosine infusion PtO2 was increased at MABP-levels of 60 and 30 mmHg, while at 20 mmHg a decrease was seen in all animals. After discontinuation of the adenosine infusion, PtO2 values were higher than those measured at the initial normotension, a similar rebound phenomenon as seen with rCBF. During the experiments all hypotensive levels could be maintained at constant level without progressively increasing infusion rates, indicating no tachyphylaxis during these time periods. After discontinuation of the drug, blood pressure did not fully reach pre-hypotensive level within 10 min. Thus, hypotension induced by adenosine down to a MABP of 30 mmHg in animal experiments does not cause deterioration in either cerebral blood flow or oxygen pressure.     

Influence of elevated renin substrate on angiotensin II and arterial blood pressure in conscious mice

The present experiments were performed to determine the influence of intravenous administration of renin substrate on plasma angiotensin II levels and mean arterial blood pressure in conscious C57BL/6J mice. Mice with chronic indwelling femoral arterial and venous catheters were acutely or chronically administered intravenous doses of a synthetic peptide corresponding to the 14 amino acids on the N-terminal of angiotensinogen. A dose-dependent increase in arterial blood pressure was observed as the intravenous bolus dose of the renin substrate was increased from 0.18 to 180 nmol kg(-1) with a maximal increase in pressure of 40 +/- 3 mmHg achieved following administration of the 18 nmol kg(-1) bolus (n = 11). Additional experiments demonstrated that a sustained intravenous infusion of the renin substrate led to a long-term increase in arterial blood pressure. The continuous infusion of renin substrate at 0.05 nmol kg(-1) min(-1) for 3 days did not alter arterial blood pressure from the control level of 119 +/- 5 mmHg (n = 5); however, arterial blood pressure significantly increased to 129 +/- 6 mmHg with an infusion rate of 0.5 nmol kg(-1) min(-1) and further increased to 141 +/- 3 mmHg when the renin substrate infusion was increased to 5.0 nmol kg(-1) min(-1). Finally, the infusion of renin substrate at 5.0 nmol kg(-1) min(-1) resulted in a significant increase in plasma angiotensin II concentration from 34 +/- 6 pg ml(-1) in vehicle-infused mice to 288 +/- 109 pg ml(-1). These results demonstrate that modulation of the circulating level of angiotensinogen can alter the plasma angiotensin II level and arterial blood pressure in normal animals.     

Brain nitric oxide changes after controlled cortical impact injury in rats

Nitric oxide (NO) and the NO end products, nitrate and nitrite, were measured at the impact site after a 5-m/s, 3-mm deformation controlled cortical impact injury in rats. Immediately after the impact injury and the NO and microdialysis probes could be replaced, there was an increase from baseline in NO concentration of 83 +/- 16 (SE) nM, compared with 0.5 +/- 4 nM in the sham injured animals (P < 0.001). This marked increase in NO occurred at the time of the initial rise in blood pressure (BP) and intracranial pressure (ICP) in response to the injury. After the initial increase in BP and ICP, the BP decreased and stabilized at a value which was approximately 20 mmHg below the preinjury values, and ICP plateaued at an average value of 20 mmHg, compared with 8 mmHg in the sham-injured animals. This provided an average cerebral perfusion pressure of 40-50 mmHg, compared with 65-75 mmHg for the sham-injured animals. These values were relatively constant for the remainder of the 3-h monitoring period. The NO values also stabilized during this time period. By 1 h after the impact injury the NO concentration measured directly using the NO electrode had decreased from baseline values by an average value of 25 +/- 6 nM. NO concentration remained significantly lower than baseline values throughout the remainder of the 3-h monitoring period. The concentration of nitrate/nitrite in the dialysate fluid also decreased by an average value of 341 +/- 283 nM 20-40 min after the injury. Dialysate nitrite/nitrate concentrations remained less than the preinjury baseline values throughout the remainder of the 3-h monitoring period. Preinjury treatment with L-nitro-arginine methyl ester (L-NAME) blunted the injury-induced increase in NO and resulted in more severe immediate intracranial hypertension and more severe systemic hypotension at one hour after injury. Mortality was also 67% with L-NAME pretreatment, compared with 1% in untreated animals.     

Cardiovascular effects of fentanyl in conscious rats

The polymicrobial sepsis induced by cecal ligation and puncture (CLP) in the rat is widely used in shock research. For ethical reasons, narcotic analgesics are often administered in this model, with the potential risk of confounding effects. In conscious non-septic rats, we investigated the cardiovascular effects of a continuous i.v. infusion of fentanyl (20 microg/kg per h) administered with fluid loading (10 ml/kg per h) for 24 h, a regimen commonly applied in rat CLP. Animals were randomly allocated to receive analgesia with fluid loading (Fentanyl group), or fluid loading alone (Control). All endpoints were assessed after 24 h of infusion. At that time, Control animals had mild respiratory alkalosis, which was essentially abolished by fentanyl. Analgesia mildly elevated the plasma norepinephrine levels [median (interquartile range): Control 232 pg/ml (0-292), Fentanyl 302 pg/ml (234-676), P=0.045] but was devoid of any effect on blood pressure, heart rate, cardiac output (mean +/-SD: Control 388+/-61 ml/kg per min, Fentanyl 382+/-62 ml/kg per min, P=0.87) and indices of left ventricular function derived from high-fidelity recordings of left ventricular pressure (dP/dtmax: Control 11782+/-2324 mmHg/s, Fentanyl 12107+/-2816 mmHg/s, P=0.77). In ex vivo experiments carried out immediately after animal sacrifice, no differences were noted between the Control and Fentanyl groups in the sensitivity of endothelium-intact aortic rings to norepinephrine-induced vasoconstriction (-logEC50: Control 8.78+/-0.28, Fentanyl 8.83+/-0.26, P=0.52) or acetylcholine-induced vasodilatation (-logEC50: Control 7.00+/-0.37, Fentanyl 7.06+/-0.26+/-0.53, P=0.75). In conclusion, the present data provide no contraindication, and even some support for the ethical use of a high dose i.v. infusion of fentanyl in cardiovascular studies of conscious catheterized rats undergoing CLP or other painful procedures.     

Effect of the cytoskeletal fixation agent phalloidin on transcapillary albumin transport and interstitial fluid pressure following subdermal prostaglandin E1 administration in the rat

AIM: Lowering of interstitial fluid pressure (Pif) facilitates fluid filtration across the capillary membrane and oedema formation in acute inflammation. The cellular mechanism behind this lowering of Pif involves beta1-integrins mediating contact between dermal cells and the extracellular matrix fibres, and also the cell cytoskeleton as disruption of actin filaments using cytochalasin-D induced a lowering of Pif and oedema formation. Fixation of actin with phalloidin attenuates oedema formation and abolishes lowering of Pif in anaphylaxis in the rat. The objective of this study was to determine whether phalloidin modifies lowering of Pif and albumin extravasation in rat skin also after prostaglandin E1 (PGE1). METHODS: Pif was measured using micropipettes connected to a servo-controlled counterpressure system. Microvascular permeability was estimated as the albumin extravasation (Ealb) using radiolabelled human serum albumin. RESULTS: Subdermal injection of PGE1 (0.85 mg mL-1) lowered Pif from -0.8 +/- 0.8 mmHg (SD) in control to -3.5 +/- 0.9 mmHg (P < 0.05) within 30 min. Pre-treatment with phalloidin (500 microg kg-1) before PGE1 resulted in Pif of -1.7 +/- 1.0 mmHg (P < 0.05 compared with PGE1). Ealb after subdermal saline was 0.07 +/- 0.04 mL g-1 DW and increased to 0.32 +/- 0.32 mL g-1 DW with PGE1 (P < 0.05) but was unaffected by pre-treatment with phalloidin given before PGE1 0.32 +/- 0.35 mL g-1 DW (P > 0.05 compared with PGE1 alone). CONCLUSION: These results are consistent with the concept that the cytoskeleton actin filaments participate in control of Pif.     

Sustained increase in arterial blood pressure and vascular resistance induced by infusion of arachidonic acid in rats

The haemodynamic responses to arachidonic acid (AA) have been investigated in seven groups of anaesthetized rats. Sodium arachidonate was infused intravenously for 4 or 20 min, and arterial blood pressure was recorded continuously. Cardiac output and organ blood flow were measured by microspheres. Infusion of arachidonate caused first a fast drop in arterial blood pressure, thereafter it increased steadily for 5-15 min towards a pressure about 25 mmHg above control level. The high pressure was maintained for at least 1 h. Repeated infusions of arachidonate gave similar responses. Inhibition of cyclo-oxygenase by indomethacin prevented the initial pressure drop to arachidonate, but not the sustained increase in pressure. Arterial pressure, total vascular resistance and blood flow in the kidneys, adrenals and spleen were significantly reduced, whereas cardiac output was not changed 4 min after start infusion of arachidonate. However, average blood pressure was significantly increased 22 and 35 min after start infusion (from 103.9 +/- 2.9 to 128.1 +/- 6.1 and 135.8 +/- 4.6 mmHg). Mean vascular resistance increased simultaneously (from 3.5 +/- 0.2 to 4.7 +/- 0.4 and 5.2 +/- 0.4 mmHg 100 mL-1), while cardiac output, stroke volume and heart rate were maintained or slightly reduced. The renal blood flow was significantly lowered (from average 4.9 +/- 0.1 to 3.3 +/- 0.2 and 4.0 +/- 0.2 mL min-1). Indomethacin did not prevent the changes in vascular resistance or organ blood flow recorded after 20-35 min. On the other hand, inhibition of both cyclo-oxygenase, lipoxygenase and the cytochrome P450 pathways by eicosatetrayonic acid (ETYA) normalized all haemodynamic parameters. Likewise, the rise in pressure was prevented by 17-octadecynoic acid (17-ODYA), an inhibitor of the cytochrome P450 enzyme activity. Thus, arachidonate infusion caused a transient decrease, and then a sustained increase in arterial pressure and vascular resistance, and a long-lasting reduction in renal blood flow, possibly owing to release of a cytochrome P450 dependent vasoconstrictor metabolite of AA.     

Angiotensin causes vasoconstriction during hemorrhage in baroreceptor-denervated dogs

The participation of angiotensin II (ANG II) in the maintenance of arterial blood pressure during hypotensive hemorrhage was examined in unanesthetized, baroreceptor-denervated dogs. When mean aortic blood pressure was reduced to 69.0 +/- 2.2 mmHg, plasma renin activity increased from 0.6 +/- 0.3 ng ANG I X ml-1 X h-1 during the prehemorrhage control period to 4.5 +/- 1.6. Twenty minutes after the hemorrhage, mean aortic blood pressure rose to 78.9 +/- 3.1 mmHg. Subsequent infusion of the angiotensin II antagonist saralasin (5.2-14.0 micrograms X kg-1 X min-1) decreased mean aortic pressure to 59.6 +/- 3.3 mmHg. When 5% dextrose was infused in place of saralasin, mean aortic pressure was 79.3 +/- 4.3 mmHg. The lower aortic blood pressure caused by saralasin infusion was the result of a significant decrease in total peripheral resistance. Resistance was 10.3 +/- 3.2 mmHg X l-1 X min lower during saralasin infusion than during dextrose infusion. We conclude that baroreceptor reflexes are not essential for the elevation of plasma renin activity during hemorrhage. In baroreceptor-denervated dogs subjected to hypotensive hemorrhage, the increased formation of ANG II has a vasoconstrictor action that contributes to the maintenance of arterial blood pressure.     

Changes in brain surface and cisternal fluid pH during Na-pentobarbital induced cardiac arrest in dogs

This paper describes the changes in the brain surface pH and cisternal cerebrospinal fluid (CSF) acid-base variables during Na-pentobarbital induced cardiac arrest in anesthetized dogs. Brain surface pH, reflecting brain extracellular fluid (ECF) pH was measured by rapidly responding flat surface pH electrodes. Cardiac arrest was induced by intravenous injection of large amounts of Na-pentobarbital (60 to 400 mg/kg). The mean arterial blood pressure fell from 138 +/- 20.8 (mean +/- 1 SD; n = 5) to 33.0 +/- 9.8 mmHg within 30 s after bolus injection of pentobarbital, indicating a rapid fall in cerebral blood flow. Brain surface pH fell abruptly and profoundly; 1 1/2 and 3 min after induction of cardiac arrest, the mean pH had fallen from 7.34 to, respectively, 7.05 and 6.81. Cisternal CSF pH changes were considerably slow with the mean pH falling from 7.35 to 7.00, 10 min after induction of cardiac arrest. This study demonstrates that during stagnant hypoxia there is abrupt and profound cerebral acidosis; more importantly, however, the data indicate that cisternal CSF pH changes lag behind brain ECF pH changes under such circumstances; analysis of cisternal CSF will grossly underestimate the magnitude of severity of brain metabolic derangement up to 10 min after cardiac arrest.     

Lack of interaction between adenosine-induced vasodilatation and carotid baroreflex-induced changes in sympathetic activity in dog hindlimb artery

In anaesthetized dogs, a hindlimb was vascularly isolated and perfused at a constant flow rate of 7.7 +/- 1.9 ml min-1 100 g-1 (mean +/- S.E.M.; n = 5) through the femoral artery. The carotid sinuses were isolated and perfused at high (greater than 145 mmHg) or low (less than 75 mmHg) pressure to enable reflex sympathetic tone on the hindlimb vessels to be controlled. Both vagi were sectioned in the neck and mean aortic blood pressure was held constant by connection of the aorta to a reservoir. The responses to infusion of three doses of adenosine at high and low carotid sinus pressures were not significantly different: infusion of 0.60 +/- 0.16 microM-adenosine reduced femoral arterial perfusion pressure (FAPP) by 11.6 +/- 3.2% (n = 6) at high carotid sinus pressure and by 12.6 +/- 5.1% (n = 4) at low carotid sinus pressure, while 4.71 +/- 0.49 microM-adenosine reduced FAPP by 20.8 +/- 4.8% (n = 6) at high carotid sinus pressure and by 20.7 +/- 4.8% (n = 6) at low carotid sinus pressure; 50.1 +/- 7.3 microM-adenosine reduced FAPP by 36.7 +/- 5.5% (n = 6) at high carotid sinus pressure and by 27.7 +/- 7.8% (n = 5) at low carotid sinus pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased pressure in venous sinusoids during decongestion of rat nasal rnucosa induced by adrenergic agonists

The haemodynamic effects of sympathetic agonists causing decongestion of the nasal mucosa have been investigated in rats. Access to mucosa was obtained from the dorsal side through a small cavity drilled in the nasal bone. The pressures in the venous sinusoids and in the interstitial fluid of nasal mucosa were recorded by micropuncture technique. The local red cell flux (LDF) was monitored by laser Doppler flowmetry, and the blood volume in the mucosa was measured by radio-labelled erythrocytes and albumin. In control rats the tissue blood volume was 0.25 ± 0.03 g (g wet wt)^-1. The interstitial fluid pressure (IFP) was 2.4± 0.6 mmHg and the average blood pressure in venous sinusoids (P_s) was 12.8 ± 2.7 mmHg. After topical application of noradrenaline (NA) the local blood volume was reduced to 0.12 ± 0.03 g g^-l. P, was increased to 18.0 ± 4.0 mmHg, whereas IFP was maintained and LDF was reduced to 40.4% of control, indicating a greater rise in post than in presinusoid vascular resistance. Blocking of both α₁, and α₂,-receptors by phentolamine caused a rise in mucosa blood volume and in LDF by 16 and 20% of control, respectively. P_s, increased significantly to 15.2 ±3.3 mmHg. Specific stimulation or blocking of α₁,-receptors by phenylephrine or prazosin induced similar or slightly smaller vascular responses than NA or phentolamine. The effects of the specific α₂-agonist (clonidine) or antagonist (yohimbine) on rat mucosa were small, indicating a domination of the α₁,-receptors. Thus, application of NA caused a rise in blood pressure in the venous sinusoids of nasal mucosa. As LDF fell simultaneously, the reduced blood volume must be due to an increased tone in the muscular wall of venous sinusoids.     

Changes in blood pressure and muscle sympathetic nerve activity during water drinking in humans

To investigate the possible involvement of the sympathetic nervous system in pressor response during water drinking, muscle sympathetic nerve activity (MSNA), blood pressure (BP), and heart rate (HR) were continuously measured in healthy young volunteers throughout the experiments of a 5-min control, 2 min of drinking 500 ml water, and a 28-min recovery. To avoid the effects of water passing through the oropharyngeal and esophageal regions and/or effects of swallowing, an equal amount of water was directly infused to the stomach through a stomach tube for 2 min. Water drinking caused a transient increase in mean arterial pressure (MAP) and HR immediately after drinking (DeltaMAP, 12.6 +/- 2.1 mmHg; DeltaHR, +19.9 +/- 1.7 beats/min at the peak). An abrupt decrease of MSNA was observed directly during water drinking (Deltaburst rate, -6.9 +/- 1.3 bursts/min; Deltatotal activity, -2,606 +/- 491 U/min), and it increased to the baseline level thereafter. Gastric infusion had little or no effect on MAP, HR, and MSNA. The present study demonstrated that a pressor response during water drinking was associated with the attenuation of MSNA and not generated by gastric infusion of water at the same rate as in this drinking manner. In conclusion, the rapid rise in BP might be caused through stimulations from the oropharyngeal region, swallowing-induced factors, and/or a feedforward mechanism by a central descending signal from the higher brain centers.     

Effects of centrally administered losartan on deoxycorticosterone-salt hypertension rats

To investigate whether brain AT1 receptor stimulation contributes as a hypertensive mechanism to deoxycorticosterone acetate (DOCA)-salt hypertension, losartan (1 mg/4 microL) or artificial cerebrospinal fluid (aCSF) was injected into the lateral cerebral ventricle in conscious control uninephrectomized Wistar rats or rats with DOCA-salt for 2 or 4 weeks, and mean arterial pressure (MAP) and heart rates (HR) were recorded. In rats with DOCA-salt treatment, resting MAP increased to 144+/-6 mmHg after 2 weeks and to 170+/-5 mmHg after 4 weeks versus 115- 120 mmHg in controls. In rats with 2 week DOCA-salt treatment, MAP started declining at 4 hr after intracerebroventricular (icv) injection of losartan, and significant decreases in MAP were found at 18 and 24 hr. In rats with 4 week DOCA-salt treatment, MAP was significantly decreased at 4, 18 and 24 hr. In both groups MAP decreased to that of control rats. In control rats, icv losartan had no effect on MAP and HR. Icv aCSF did not significantly change MAP and HR in either DOCA-salt hypertensive rats or control rats. Normalization of MAP after icv administration of the AT1 receptor antagonist suggests a significant role for brain AT1 receptor stimulation in the development and maintenance of hypertension in the DOCA-salt hypertensive rat model.     

Pulmonary hemodynamic effects of intravenous almitrine in patients with chronic bronchitis and respiratory insufficiency

The effects on ventilation, gas exchange and pulmonary haemodynamics of 1 h infusion of 0.5 mg X kg-1 almitrine (Vectarion) were studied in 14 patients with chronic bronchitis, with clear hypoxemia (PaO2 less than 65 mmHg) and hypercapnia (PaCO2 greater than or equal to 45 mmHg). The separate effects of the almitrine solvent and/or the solution were studied in six similar chronic bronchitics. In this latter group, blood gases and haemodynamic values were not significantly altered. In subjects treated with almitrine, PaO2 raised from 51.9 +/- 6.6 (control: T0) to 61.9 +/- 9.9 mmHg at the 60th min (t60) of infusion (p less than 0.001); PaCO2 decreased from 52.8 +/- 6.3 (t0) to 45.7 +/- 5.2 mmHg at t60 (p less than 0.001). The effects on blood gases were still marked 10 min after infusion (t70). The significant increase in PaO2 was faster (10th min) than that of PaCO2 (20th min). The mean pulmonary artery pressure (Ppa) rose appreciably, from 27.8 +/- 11.3 at t0 to 35.5 +/- 12.5 mmHg at t60 (p less than 0.001). This rise was significant from the 10th min (p less than 0.005) and was related to that of pulmonary vascular resistance since on average cardiac output and pulmonary wedge pressure did not change. Ppa came back to its initial value at t70. Thus pulmonary vasoactive effects were at the same time early and transitory. They seemed due to an arterial vasoconstriction (role of chemoreceptors?), which could also explain the perfusion redistribution to the best ventilated areas and the improvement of VA/Q inequalities.     

Correlation of blood pressure in end-stage renal disease with platelet cytosolic free calcium concentration during treatment of renal anemia with recombinant human erythropoietin.

The hemodynamic hallmark of hypertension complicating the treatment of renal anemia with recombinant human erythropoietin (rHu-EPO) is increased total peripheral vascular resistance, but the mechanisms underlying the arteriolar vasoconstriction are still an enigma. We studied body fluid volumes, plasma renin activity, plasma norepinephrine, and calcium metabolism in platelets in 40 previously normotensive hemodialysis patients before and after 12 weeks of rHu-EPO treatment. Partial correction of anemia caused a rise in arterial pressure (94 +/- 6 mmHg vs 124 +/- 7 mmHg, p less than 0.05) and in platelet cytosolic calcium concentration (113 +/- 5 nM vs 171 +/- 18 nM, p less than 0.05) in eight patients. Hypertensive patients had significantly higher plasma noradrenaline concentrations, but they did not differ significantly in body fluid volumes and plasma renin activities. There was a close correlation between free calcium concentration in platelets and mean arterial pressure in patients developing rHu-EPO-induced-hypertension (r = 0.95). Short-term antihypertensive treatment resulted in a reduction of free calcium concentrations in platelets and a concomitant fall in blood pressure. The main results of the present studies suggest that rHu-EPO-induced hypertension might be associated with altered cellular calcium homeostasis and hyperactivity of the sympathetic nervous system. If rHu-EPO therapy induces alterations of pressor factors or the hormone itself raises the cytosolic calcium not only in platelets but also in vascular smooth muscle cells, altered cellular calcium influx may contribute to the arteriolar vasoconstriction.     

Increased negativity of interstitial fluid pressure contributes to development of oedema in rat skin following application of xylene.

Intradermal interstitial fluid pressure (Pi) has been studied in rat skin during formation of inflammatory oedema caused by application of xylene. Pi was measured with sharpened micropipettes connected to a servocontrolled counter-pressure system. Control Pi averaged -1.3 +/- 0.6 (SD) mmHg. Following xylene application Pi decreased to -5.0 mmHg after 5 min and then increased to stabilize at about 0 mmHg at 45-60 min and later. When the transvascular fluid shifts accompanying the inflammatory reaction were prevented by inducing circulatory arrest prior to xylene application, Pi fell to -7.5 mmHg within 5 min and remained at this level throughout the observation period of 90 min. Aprotinin in large doses (80,000 KIE kg-1) before xylene application reduced the fall in Pi, whereas indomethacin had no effect. The increased negativity in Pi will add directly to a normal transcapillary net filtration pressure of about 0.5 mmHg, resulting in a 10- to 20-fold increase in this pressure. The present experiments therefore suggest that the interstitium plays an active role in oedema formation in the initial phase of xylene-induced inflammation in rat skin through the development of an increased negativity of Pi.     

Application of a new technique--blood pressure clamping--for analysis of prostaglandin interference with sympathetic neurotransmission in man

To circumvent baroreceptor reflexes following drug-induced interference sympathetic neurotransmission, a new technique - blood pressure clamping--has developed. This implies that the sympathetic activity in an awake human is 'clamped' at a supranormal level by infusion of a vasodilator. In 11 healthy volunteers nitroprusside or saline was randomly infused in two consecutive 2-h periods. Plasma and urinary catecholamine levels were analysed by liquid chromatography. The experiments were repeated after random administration of the prostaglandin synthesis inhibitor, ibuprofen, or placebo. In the basal state (no ibuprofen, saline infusion) the mean arterial blood pressure was 81.4 +/- 2.3 mmHg, the heart rate was 60.9 +/- 0.3 beats min-1 and the plasma level of noradrenaline was 1.12 +/- 0.15 nM. Infusion of nitroprusside at a dose lowering the mean blood pressure by 11.6 +/- 1.6 mmHg and increasing the heart rate to 74.6 +/- 2.9 beats min-1 elevated plasma noradrenaline to 2.86 +/- 0.39 nM. After pretreatment with ibuprofen (saline infusion), the systemic blood pressure, the heart rate, and the plasma and urinary levels of noradrenaline were unaffected in comparison to before drug (80.1 +/- 2.3 mmHg, 58.4 +/- 0.3 beats min-1 and 1.13 +/- 0.12 nM respectively). Infusion of nitroprusside at a rate lowering the blood pressure by 11.2 +/- 2.4 mmHg and increasing the heart rate to 74.4 +/- 0.5 beats min-1, elevated the plasma level of noradrenaline to 2.46 +/- 0.38 ng ml-1, which is not different from before ibuprofen. The amount of nitroprusside required to lower the blood pressure was not different in the presence and absence of ibuprofen.(ABSTRACT TRUNCATED AT 250 WORDS)