Influence of neurohumoral blockade on heart rate and blood pressure responses to haemorrhage in isoflurane anaesthetized rats

Four groups of Sprague-Dawley rats were anaesthetized with isoflurane (ISO) (1.7% end-tidal concentration) in 40% oxygen, and mechanically ventilated. The animals were bled 15 mL kg-1 b.w. from the femoral vein over 10 min, followed by an observation period of 30 min. Ten minutes before haemorrhage each group of animals was pre-treated with intravenous injection/infusion of either: isotonic saline (Group B; CON; n=7), vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)AVP; 10 microg kg-1] (Group C; AVP-a; n=7), the non-selective angiotensin II receptor antagonist saralasin (10 microg kg-1 min-1) (Group D; SAR; n=7) or hexamethonium (10 mg kg-1) (Group E; HEX; n=7). A separate group of conscious animals were pre-treated with isotonic NaCl and subjected to the same haemorrhage protocol (Group A; AW; n=7). Mean arterial pressure (MAP), heart rate (HR) and blood gases were observed during the experiments. Only pre-treatment with SAR and HEX reduced MAP significantly. The pre-haemorrhage HR was only affected by HEX, which caused a reduction by 17%. The HR was significantly lower at the end of haemorrhage compared with pre-haemorrhage levels in all groups except that group treated with HEX. In that group the HR changed in the opposite direction. The ability to maintain MAP during haemorrhage, and the post-haemorrhage period, was significantly impaired in the groups treated with AVP-a, SAR or HEX compared with the group receiving NaCl. It is concluded that autonomic nervous activity is of major importance for the maintenance of MAP during isoflurane anaesthesia, whereas circulating angiotensin II and vasopressin levels contribute to a much smaller degree in this regard. General anaesthesia in combination with different degrees of neurohumoral blockade impairs the haemodynamic responses to blood loss, seen in conscious individuals. The impairment involves both the early and late phases during haemorrhage, as well as the post-bleeding recovery period. All three neurohumoral systems (autonomic nervous activity, angiotensin II and vasopressin) are of importance for regulating MAP during and after haemorrhage, although the autonomic nervous outflow appears to contribute to a larger extent.     

Increased resistance to haemorrhage induced by intracerebroventricular infusion of hypertonic NaCl in conscious sheep.

The effect of elevated cerebrospinal fluid Na+ concentration (CSF [Na+]) on the tolerance of blood loss, and concomitant cardiovascular and humoral responses were studied in conscious sheep. A slow (0.7 ml kg-1 min-1) venous haemorrhage was continued until the mean systemic arterial pressure suddenly decreased to less than 50 mmHg, or in the absence of hypotension, until a total blood loss of 25 ml kg-1. Significantly more blood had to be removed to induce hypotension in animals receiving an intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of 0.5 M NaCl (starting 30 min before haemorrhage and continued throughout the experiment) compared to control haemorrhages without concomitant i.c.v. infusion (22.7 +/- 1.2 ml vs 16.9 +/- 0.9 ml kg-1). In one animal, subjected to 0.5 M NaCl infusion, the blood pressure was still maintained at 25 ml kg-1 of haemorrhage. In spite of a larger blood loss, animals receiving i.c.v. infusion of hypertonic NaCl had an improved recovery of the blood pressure after haemorrhage, due to a better maintained cardiac output rather than to a reinforced increase of the vascular resistance. The improved cardiovascular responses to haemorrhage during elevated CSF [Na+] are not readily explained by the effects on the plasma concentrations of vasopressin, angiotensin II or noradrenaline, although the latter was augmented. The plasma protein concentration decreased already during the 30 min of hypertonic NaCl infusion preceding haemorrhage, and the haemodilution caused by the subsequent blood removal was aggravated, which indicates that this treatment also causes transfer of fluid to the plasma compartment. We conclude that elevated CSF [Na+] increases tolerance to haemorrhage and improves cardiovascular function after blood loss in sheep. Since the haemodynamic responses in many respects were similar to those reported in response to the systemic administration of a small volume of hypertonic NaCl solution in haemorrhagic shock, part of the effect of that treatment may be mediated via cerebral effects of increased Na+ concentration.     

Intracerebroventricular angiotensin II increases tolerance to blood loss in conscious sheep

Intracerebroventricular (i.c.v.) infusion of hypertonic NaCl improves the tolerance to haemorrhage in sheep. Since i.c.v. angiotensin II (ANG II) shares many of the effects of hypertonic NaCl on fluid balance control and blood pressure, we aimed to determine whether i.c.v. ANG II would also be effective in that regard. Six adult conscious ewes were bled from the jugular vein until the mean arterial pressure suddenly dropped to between 45 and 50 mmHg, during an i.c.v. infusion of ANG II (2 pmol kg^-1 min^-1) which commenced 30 min prior to start of blood removal and continued until end of retransfusion about 80 min after haemorrhage. A corresponding haemorrhage in the same animals during an i.c.v. infusion of 0.9% NaCl served as controls. Significantly more blood had to be withdrawn to induce hypotension when ANG II was given i.c.v. (22.3±1.8 vs. 12.6±1.2 mL kg^-1). The degree of hypotension and the recovery rate of the blood pressure did not differ between the experiments. The increased tolerance to blood loss by ANG II i.c.v. was accompanied by a reinforced elevation of the systemic vascular resistance and a larger decline of the cardiac output. The plasma norepinephrine concentration was significantly increased immediately after haemorrhage during i.c.v. ANG II, but not in control experiments. The overall vasopressin response to the hypotensive blood loss was not affected by ANG II, but high plasma levels were obtained already during the non-hypotensive stage of haemorrhage. The i.c.v. infusion of ANG II caused a significant lowering of the plasma protein concentration before start of bleeding and accentuated the haemodilution caused by the haemorrhage. We conclude that central administration of ANG II increases the tolerance to haemorrhage in sheep but with concomitant haemodynamic changes which appear unfavourable regarding cardiac load and tissue perfusion.     

The role of tumour necrosis factor-alpha in renal dysfunction following mild haemorrhage in rats

Mild haemorrhage occasionally causes delayed death following failure of kidney or multiple organs, but the precise mechanisms have not yet been identified. We investigated the role of tumour necrosis factor-alpha (TNF-alpha), known as a major pro-inflammatory cytokine that leads to multiple organ failure, on the renal damage induced by mild haemorrhage. A mild haemorrhagic state was induced in male anaesthetized rats by bleeding via a common carotid catheter for 20 min at 16.7% of total body blood, 1.09 ml/100 g body weight, without fluid resuscitation. Mean arterial pressure and heart rate decreased soon after haemorrhaging but returned to baseline level up to 5 h after bleeding. TNF-alpha mRNA expression in the kidney and serum TNF-alpha levels were highest at 1 h after bleeding. Intraperitoneal pretreatment with FR167653, an inhibitory compound of TNF-alpha production, as well as of interleukin (IL)-1beta, significantly inhibited the increase in TNF-alpha. The inflammatory cell infiltration and tubular cell injury induced by haemorrhage were suppressed, and the renal dysfunction was dramatically improved by the FR167653 treatment. The morphological changes were also less in the treated group than in those that had not been treated. TNF-alpha has been reported to have striking effects on IL-1beta release and activation of neutrophils, and to play a pivotal role in the expression of the other pro-inflammatory cytokines. Our data show that endogenously-derived TNF-alpha does play a key role in the renal dysfunction during mild haemorrhage. These results should be useful to forensic pathologists to explain the pathogenesis of renal dysfunction induced by a mild haemorrhage and to identify the cause of death where there are no significant morphological changes after mild haemorrhage.     

Difference between hypertonic NaCl and NaHCO3 as osmotic diuretics in dog kidneys

To compare the osmotic inhibitory effects of NaCl and NaHCO3 on proximal tubular fluid reabsorption, plasma osmolality was raised by 40 mosmol kg-1 H2O by infusing hypertonic NaCl and NaHCO3 in volume-expanded dogs receiving ethacrynic acid. In five dogs studied at constant plasma pH 7.5, both NaCl and NaHCO3 reduced water reabsorption by 29 +/- 2%. However, NaCl infusion reduced bicarbonate reabsorption by 31 +/- 2%, whereas bicarbonate reabsorption remained unchanged during NaHCO3 infusion. In six dogs, bicarbonate reabsorption was kept constant during NaCl and NaHCO3 infusion by adjustments of plasma pH. At similar glomerular filtration rates (42.4 +/- 2.9 ml min-1), water reabsorption was 28.7 +/- 1.7 ml min-1 in the control period, 29.4 +/- 2.5 ml min-1 during hypertonic NaCl infusion and 20.6 +/- 1.2 ml min-1 during hypertonic NaHCO3 infusion. Therefore, NaCl did not reduce proximal tubular water reabsorption by a direct osmotic effect. By calculating the regression coefficient for the relationship between measured chloride reabsorption and maximal convective chloride flux, the effective reflection coefficient for NaCl averaged 0.11 +/- 0.01. The combination of a low reflection coefficient and high permeability may explain why hypertonic NaCl is not an osmotic diuretic.     

Cocaine-induced small vessel spasm in isolated rat hearts.

Cocaine abuse has been associated with pathologic cardiovascular events including acute myocardial infarction (AMI) and sudden death. Although coronary vasospasm has been proposed as a possible mechanism, the ability of cocaine to induce coronary spasm has not been conclusively demonstrated. In these studies, isolated rat hearts were perfused with cocaine (100 micrograms to 500 micrograms/ml) for 1 minute, perfusion-fixed with glutaraldehyde, and histologically assessed for evidence of coronary spasm through light and electron microscopy. Light micrographs revealed that cocaine induced spasm in coronary arterioles up to 65 microns in diameter, whereas larger caliber vessels did not constrict. Ultrastructurally, vacuolation was observed in the endothelial and smooth muscle cells of constricted arterioles. Endothelial integrity was maintained and interendothelial junctions remained intact. Morphologic evidence of constriction was supported by data obtained from Langendorff-heart preparations in which cocaine reduced myocardial flow rate under constant pressure conditions and increased aortic perfusion pressure under constant flow conditions. Spasm induced by cocaine was prevented by the calcium entry blocker nitrendipine, but not by phentolamine, an alpha-adrenergic antagonist. The finding of small vessel spasm in this study may explain the significant number of clinical cases of cocaine-associated AMI in which the main coronary arteries appear angiographically normal.     

Correlation of the directly observed responses of mesenteric vessles of the rat to nerve stimulation and noradrenaline with the distribution of adrenergic nerves

1. The effects of nerve stimulation and of the topical application of noradrenaline on arteries, capillaries and veins of the mesentery of the anaesthetized rat were examined by direct observation under a microscope. The distribution of adrenergic nerves to the vessels of the mesentery was studied using the fluorescence histochemical method.2. Principal arteries, small arteries and terminal arterioles were all innervated by a network of adrenergic fibres and they all constricted in response to the stimulation of paravascular nerves and to exogenous noradrenaline. Few adrenergic fibres accompanied the smaller, precapillary arterioles; these vessels did not respond to nerve stimulation, although they were constricted by concentrations of noradrenaline as low as 10(-10) g/ml.3. The capillaries did not respond to nerve stimulation or to applied noradrenaline. All veins were constricted by noradrenaline, but only those veins greater than about 30 mum in internal diameter responded to nerve stimulation.4. At stimulus frequencies greater than 4 Hz the flow of blood through the microvasculature usually ceased, although there was never complete closure of these vessels. The maximum constriction observed in principal arteries was usually between 50 and 70% of the control internal diameter, and in small arteries and terminal arterioles was between 40 and 65% of the control internal diameter.5. It is concluded that the principal arteries and small arteries of the mesenteric vasculature are important in the control of blood flow through this vascular bed during sympathetic stimulation and following topical application of noradrenaline, and that the precapillary arterioles are important vessels determining the rate of blood flow through the capillary bed under resting conditions.     

高渗氯化钠对兔失血性休克时肾形态的影响—超微结构观察

本文从超微结构水平描述了两种氯化钠溶液对休克肾的作用。结果说明,高渗氯化钠对休克肾的微血管、肾单位各部均有明显的保护作用,为临床应用提供某些形态学依据。     

Correlation of the directly observed responses of mesenteric vessels of the rat to nerve stimulation and noradrenaline with the distribution of adrenergic nerves

1. The effects of nerve stimulation and of the topical application of noradrenaline on arteries, capillaries and veins of the mesentery of the anaesthetized rat were examined by direct observation under a microscope. The distribution of adrenergic nerves to the vessels of the mesentery was studied using the fluorescence histochemical method.

2. Principal arteries, small arteries and terminal arterioles were all innervated by a network of adrenergic fibres and they all constricted in response to the stimulation of paravascular nerves and to exogenous noradrenaline. Few adrenergic fibres accompanied the smaller, precapillary arterioles; these vessels did not respond to nerve stimulation, although they were constricted by concentrations of noradrenaline as low as 10^-10 g/ml.

3. The capillaries did not respond to nerve stimulation or to applied noradrenaline. All veins were constricted by noradrenaline, but only those veins greater than about 30 μm in internal diameter responded to nerve stimulation.

4. At stimulus frequencies greater than 4 Hz the flow of blood through the microvasculature usually ceased, although there was never complete closure of these vessels. The maximum constriction observed in principal arteries was usually between 50 and 70% of the control internal diameter, and in small arteries and terminal arterioles was between 40 and 65% of the control internal diameter.

5. It is concluded that the principal arteries and small arteries of the mesenteric vasculature are important in the control of blood flow through this vascular bed during sympathetic stimulation and following topical application of noradrenaline, and that the precapillary arterioles are important vessels determining the rate of blood flow through the capillary bed under resting conditions.

     

Responses of cerebral arteries and arterioles to acute hypotension and hypertension

The responses of cerebral precapillary vessels to changes in arterial blood pressure were studied in anesthetized cats equipped with cranial windows for the direct observation of the pial microcirculation of the parietal cortex. Vessel responses were found to be size dependent. Between mean arterial pressures of 110 and 160 mmHg autoregulatory adjustments in caliber, e.g., constriction when the pressure rose and dilation when the pressure decreased, occurred only in vessels larger than 200 micron in diameter. Small arterioles, less than 100 micron in diameter, dilated only at pressures equal to or less than 90 mmHg; below 70 mmHg their dilation exceeded that of the larger vessels. When pressure rose to 170- 200 mmHg, small vessels dilated while the larger vessels remained constricted. At very high pressures (greater than 200 mmHg) forced dilation was frequently irreversible and was accompanied by loss of responsiveness to hypocapnia. Measurement of the pressure differences across various segments of the cerebral vascular bed showed that the larger surface cerebral vessels, extending from the circle of Willis to pial arteries 200 micron in diameter, were primarily responsible for the adjustments in flow over most of the pressure range.     

Effects of haemorrhage on the distribution of the peripheral blood flow in the rabbit

1. The effects of bleeding unanaesthetized rabbits by 26% of their blood volume on the blood flow in the portal, renal, muscle and skin beds were investigated in normal animals, in animals without functioning autonomic effectors, and in animals with section of the carotid sinus and aortic nerves.2. In animals without functioning autonomic effectors there was progressive vasodilatation during the 4 hr following haemorrhage, which differed markedly in the different regional beds studied. The dilatation was greatest in the portal bed, followed by kidney and skin, but there was no significant change in the vascular resistance in muscle.3. In normal animals with intact reflexes the vascular resistance either increases or remains at control values, suggesting that reflex constrictor effects oppose locally acting dilator mechanisms. During the 4 hr following haemorrhage reflex vasoconstrictor effects were greatest in kidney, followed by muscle, portal bed and skin.4. In animals with section of the carotid sinus and aortic nerves reflex constrictor effects were absent in the portal, muscle and skin beds, but significant vasoconstriction was still evident in the renal bed, though of smaller magnitude than in normal animals. The results suggest that the arterial baroreceptors are a major source of reflex activity following haemorrhage, but that other reflexogenic zones contribute to the renal effects in normal animals.     

Micropuncture evaluation of the importance of perivascular pH for the arteriolar diameter on the brain surface

Summary A micropipette technique was used to induce local changes of the bicarbonate concentration of the cerebro-spinal fluid surrounding arterioles on the exposed cerebral cortex of anaesthetized rats and cats. Injection volumes of a few nanoliters caused circumscribed and pronounced changes of the diameter of the arterioles under study: mock spinal fluid without bicarbonate dilated, while a solution containing 25 meq/l of bicarbonate constricted the vessels. In such experiments the localpCO₂ of the arteriolar wall remains practically constant, since it is set by thepCO₂ of the arterial blood and of the cerebral tissue. Hence the microinjections essentially consisted in a local change of the pH of the fluid surrounding a small segment of a cerebral arteriole. Since metabolic changes of the nervous tissue changes the periarteriolar pH, it is probable that local pH induced vasomotor changes of the type reported here participate in the so called metabolic regulation of the cerebral blood flow which underlies the local adaptation of the cerebral blood flow to changing functional demands.Supported by the Deutsche Forschungsgemeinschaft.     

Inefficiency of intracerebroventricular ANP to alter haemodynamic,plasma vasopressin and renin responses to haemorrhage in sheep

Whether intracerebroventricular (i.e.v.) infusion of atrial natriuretic peptide (human-ANP, 1–28) 25 pmol min^-1 influences the tolerance to blood loss and haemorrhage induced cardiovascular, vasopressin and renin responses were studied in five conscious sheep. The i.e. v. infusion was started 60 min prior to a slow (0.7 ml kg^-1 min^-1) venous haemorrhage, was run concurrently with bleeding, and for 90 min thereafter. Venous blood was removed until the mean systemic arterial pressure suddenly fell to about 50 mmHg. There were no statistically significant differences in either the bleeding volume necessary to induce the sudden decrease in blood pressure, or in cardiovascular parameters measured by venous heart thermodilution catheterization, compared with control experiments with i.e.v. infusion of artificial CSF. The plasma protein and vasopressin concentrations and renin activity were unaffected by the i.c.v. infusion of ANP as were the changes in these parameters occurring during the subsequent haemorrhage. The same negative findings were obtained with a three times higher dose of ANP(l-28) (75 pmol min^-1), tested in three of the animals. Thus the i.c.v. infusion of ANP(l-28), in amounts expected to elevate the CSF concentration far above basal levels does apparently not influence normal blood pressure regulation or alter haemodynamic, vasopressin and renin responses to haemorrhage in conscious sheep.     

Endothelial cell helix in small arterioles of human ureters. A study by scanning electron microscopy (SEM).

Microvessel corrosion casts of human ureters were prepared. Portions of casts were longitudinally cut by use of a pulsed Eximer laser beam in order to get insight into microvessel branches studied in SEM. Larger arterioles (greater than 30 microns in diameter) showed oval imprints of endothelial cell nuclei along the vessel axis. Imprints were found in furrows parallel to resin ridges. Smaller arterioles (less than microns in diameter) displayed imprints of nuclei aligned in a helix around the vessel axis. With regard to capillaries, one nucleus imprint was spaced far apart from the other. Venules demonstrated a reticular network of thick, attenuated resin ridges and of small meshes which consisted of round or oval nucleus imprints. It is concluded that smaller arterioles form an endothelial cells helix.     

Paediatric pulmonary haemorrhage: Independent lung ventilation as effective strategy in management

Pulmonary haemorrhage is an uncommon symptom in paediatrics with the etiology varying among the series by age, location, and the diagnostic tests employed. Once airway protection and volume resuscitation are ensured, localization of the anatomic site of bleeding, isolation of the involved airway, control of haemorrhage and treatment of the underlying cause of becomes essential. In localized persistent bleeding, airway control may be achieved by lung isolation with double lumen endotracheal tube and synchronous independent lung ventilation     

Tortuosity of terminal arterioles in the basal ganglia is increased in status lacunaris

The goal of this study was to evaluate the participation of small (diameter between 26 microns and 90 microns) and terminal (diameter between 10 microns and 25 microns) arterioles in the status lacunaris of the basal ganglia and to classify tortuous vascular profiles based on morphometry. Paraffin sections, 40 microns thick, of the basal ganglia from autopsied patients over the age of 45, were stained with PAS. A three-dimensional microscope, R400 (edge) was used to evaluate the structure of the blood vessels. Six patterns of the tortuous profiles were identified: simple kink, loop, knot, tangle, coil, and wave, and well as their combinations. Tortuous arterioles in the basal ganglia were present both in control group and status lacunaris cases. However, statistical Student's t-test analysis revealed a significant increment in the number of microfields containing tortuous terminal arterioles in the status lacunaris group (mean 7.50 +/- 4.62) versus the control group (mean 2.92 +/- 1.38) (p = 0.001). A risk for status lacunaris was associated with the increased frequency of tortuous terminal arterioles (Odd ratio = 1.94, 95%-Confidence Interval = 1.17-3.22) (p = 0.008) but not small arterioles (Odd ratio = 1.64, 95%-Confidence Interval = 0.62-4.38) (p = 0.39). Our findings suggest than an increased number of tortuous terminal arterioles is associated with status lacunaris. Six characteristic patterns of the tortuous profiles as well as their combinations were identified.     

高渗氯化钠-醋酸钠溶液改善失血性休克大鼠微循环的作用

目的：研究高渗氯化钠－醋酸钠溶液对失血性休克大鼠微循环的作用。方法：ＳＤ大鼠随机分为７．５％ＮａＣｌ（ＨＳ）、５％ＮａＣＬ－３．５％ＮａＡｃ（ＨＳＡ）、０．９％ＮａＣｌ（ＮＳ）三组。休克模型完成后,分别按４ｍＬ／ｋｇ给药,观察脊斜肌微循环的变化。测定局部用药后,ＨＳ和ＨＳＡ对血管内径的直接作用,结果：ＨＳ较ＨＳＡ更为显著升高ＭＡＰ。给药５ｍｉｎ,ＨＳＡ、粪土中脊斜肌第三级细动静脉内径、血流速度、血     

Rearrangement of the metaphyseal vasculature of the rat growth plate in rickets and rachitic reversal: a model of vascular arrest and angiogenesis renewed.

The morphology of the metaphyseal microvasculature at the epiphysis was examined at both the light and electron microscopic level in rickets and rachitic reversal. The animals studied were normal, rachitic, and rachitic reversed at 8, 24, and 96 hours post-vitamin D administration. The overall architecture of the metaphyseal vessels was significantly altered throughout the intervals examined. In the rachitic animal, arterioles, venules, and capillaries were found adjacent to the growth plate, either directly apposed to the hypertrophic chondrocytes or separated from them by bone-forming cells. These vessels are in many ways similar to the larger arterioles and venules that normally supply the metaphyseal capillary sprouts, but in the normal growing animal are usually located 350-500 microns from the epiphyseal cartilage. The rachitic capillaries appear relatively well differentiated with a partial basement membrane and a perivascular cell lining. In early rachitic reversal, small vascular projections are induced to grow from the large diameter venules that border upon the hypertrophic chondrocytes. These vascular sprouts that invade the epiphyseal cartilage are quite undifferentiated, with no basement membrane or pericyte lining at the sprout apex and occasional abluminal endothelial cell projections. Within 96 hours, the metaphyseal microvasculature has returned to an apparently normal state with only capillaries at the cartilage-vascular interface and larger vessels (arterioles and venules) located several hundred microns deeper into the metaphysis. The sequential processes of differentiation and cessation of capillary growth followed by dedifferentiation and reinitiation of microvascular growth make the rachitic system a unique one in which to study angiogenesis.     

Mechanism of osmotic diuresis studied by infusion of NaHCO3 and mannitol in dogs

To examine whether mannitol and NaHCO3 are equally potent inhibitors of proximal tubular fluid reabsorption, experiments were performed in 10 anaesthetized volume-expanded dogs during continuous infusion of ethacrynic acid. At plasma pH 7.5, a rise in plasma osmolality of 40 mosmol kg-1 reduced the remaining tubular fluid reabsorption in five dogs by 14 +/- 3% during NaHCO3 infusion and by 28 +/- 1% during mannitol infusion. Bicarbonate reabsorption increased by 25 +/- 5% during NaHCO3 infusion and decreased by 14 +/- 1% during mannitol infusion. At equal rates of bicarbonate reabsorption the inhibitory effects on tubular fluid and NaCl reabsorption were slightly less during mannitol than during NaHCO3 infusion. In five other dogs studied at constant plasma concentration of sodium, changes in bicarbonate reabsorption were avoided by raising plasma pH to 7.7 during NaHCO3 infusion and by reducing plasma pH to 7.4 during mannitol infusion. Tubular fluid reabsorption was reduced 32 +/- 4% by NaHCO3 and 34 +/- 4% by mannitol infusion, indicating equal inhibitory effects. The mechanism may be that the osmotic force for paracellular reabsorption of water and NaCl across the tight junction is equally reduced by equiosmolal increments in the NaHCO3 and mannitol concentration of the proximal tubular fluid.     

Evidence for an influence of CSF sodium concentration upon ACTH-mediated cortisol response to intravenous and intracerebroventricular angiotensin II

The influence of cerebrospinal fluid (CSF) NaCl concentration upon the cortisol release induced by intracerebroventricular (i.c.v.) and intravenous (i.v.) infusions of angiotensin II (AII) was studied in conscious goats. A first series of experiments involved i.c.v. infusion (20 min; 20 microliters min-1) of simply hypertonic (0.5 M) NaCl, or of AII (2 pmol kg-1 min-1) dissolved in 0.5 M or isotonic (0.15 M) NaCl or in isotonic glucose. The most pronounced rise in plasma cortisol concentration (PC) was elicited by AII in 0.5 M NaCl, but responses of nearly the same size were obtained by merely 0.5 M NaCl and by AII in isotonic NaCl, whereas AII in glucose induced a smaller PC rise. An urge to drink developed during all infusions, except during the AII/glucose infusion. Here, however, thirst became apparent 2-6 min post-infusion. When, in a second series, the hypertonicity of the NaCl was reduced to 0.3 M, and the dose of AII to 0.5 pmol kg-1 min-1, only the infusion of AII in 0.3 M NaCl elicited any appreciable rise in PC. The response was approximately the same size as that earlier obtained as the effect of the larger dose of AII dissolved in isotonic saline. In a third series of experiments, a 30-min i.c.v. infusion of isotonic glucose, preceding and out-lasting a 10-min i.v. infusion of AII (40 pmol kg-1 min-1), was found to extinguish the rise in PC obtained as the effect of a separate i.v. infusion of AII.(ABSTRACT TRUNCATED AT 250 WORDS)