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Biomedical subjects

D A Denton

Publications and source records attributed to D A Denton.

At least 91 records · Page 5Linked to original sources
PubMed1987

Role of the autonomic nervous system, renin-angiotensin system, and arginine vasopressin during the onset and maintenance of ACTH hypertension in sheep.

The roles of the autonomic nervous system, renin-angiotensin system, and arginine vasopressin (AVP) during the onset of ACTH-induced hypertension were investigated in conscious sheep. Autonomic ganglion blockade or combined adrenergic and cholinergic receptor blockade demonstrated that an intact sympathetic nervous system was not essential for the development or maintenance of the hypertension. Autonomic blockade augmented the pressor response to ACTH, indicating that baroreceptor-mediated reflexes normally operate to suppress the degree of hypertension produced by ACTH. Evidence was obtained suggesting that the renin-angiotensin system and AVP may partially contribute to the maintenance of ACTH hypertension in the presence of autonomic blockade. However, the precise mechanism by which ACTH raises arterial pressure remains to be elucidated.

Adrenocorticotropic Hormone↗
PubMed1987

Natriuresis induced by localized perfusion within the third cerebral ventricle of sheep.

Push-pull perfusion was performed at four different sites in the third cerebral ventricle of conscious sheep. The recovery of the infused solution was 75-90%, suggesting a localized change in the ionic composition and osmolality restricted to a relatively small area in the cerebrospinal fluid (CSF). Sodium and potassium excretion and urine flow were studied before, during, and after perfusion of 200, 150, and 100 mM Na-CSF. Localized perfusion in the anterior dorsal third ventricle (AD3V) of 200 mM Na-CSF caused an increase in sodium and potassium excretion, in urine flow, and a decrease in free water clearance. Perfusion of 200 mM Na-CSF at the other three perfusion sites, i.e., anterior ventral third ventricle, posterior dorsal third ventricle, and posterior ventral third ventricle, did not influence sodium excretion and urine flow. Perfusions with 150 and 100 mM Na-CSF did not cause any change in sodium, potassium excretion, or urine flow at any of the four perfusion sites. These results suggest that sensors sensitive to changes of sodium concentration are located close to the ventricular surface in the anterior dorsal part of the third cerebral ventricle. When stimulated with increased sodium concentration they will initiate increased sodium excretion.

Animals↗
PubMed1987

Role of angiotensin in sodium appetite of sodium-deplete sheep.

The role of the renin-angiotensin system (RAS) in the Na appetite of Na-deplete sheep was investigated. Intravenous infusion of the angiotensin-converting enzyme inhibitor, captopril, at 0.01 or 0.1 mg X kg-1 X h-1 did not cause any change in Na intake, although the higher dose caused a marked decrease in mean arterial blood pressure. Intravenous infusion of captopril at 1.0 mg X kg-1 X h-1 over 24 h decreased Na intake by 45-55% in the absence of any change in Na loss. The decrease in Na intake was restored to base-line level or above by concurrent intravenous infusion of angiotensin II (ANG II) at 3.8 or 24 micrograms/h over 24 h but not by intracerebroventricular (ICV) ANG II at 3.8 micrograms/h. In addition, ICV infusion of 0.7 M mannitol (1 ml/h over 3 h), which reduced cerebrospinal fluid (CSF) and brain extracellular fluid [Na], still increased Na intake when combined with intravenous captopril. Water intake was not altered during intravenous captopril or ANG II alone but was increased during ICV ANG II or 0.7 M mannitol (with or without iv captopril). In conclusion, these results suggest that the RAS is involved in the Na appetite of the Na-deplete sheep. Furthermore, it would appear that the brain area involved is one without a blood-brain barrier but with a CSF-brain barrier, such as one of the circumventricular organs. Also, it would appear that the effect of lowered cerebral Na and the effect of activation of the renin-angiotensin system on Na appetite are independent.

Angiotensin II↗
PubMed1987

Modification of the haemodynamic effects of ACTH by angiotensin II in sheep.

The study was performed to examine the hypothesis that adrenocorticotrophic hormone (ACTH) induced hypertension in sheep would be enhanced if the blood level of angiotensin II (ANG II), normally suppressed during ACTH administration, was kept at control levels by intravenous infusion of ANG II. Administration of ACTH at 1.0 microgram/kg/day for 6 days produced a half maximum rise in mean arterial pressure, delta 14 mmHg, associated with hypokalaemia and initial urinary sodium retention. A rate of ANG II infusion, (0.9 microgram/kg/day) for 6 days, was contrived to produce a small increase in peripheral resistance and mean arterial pressure, delta 10 mmHg. Pressor responses to concomitant infusion of ACTH and ANG II were additive, delta 25 mmHg. There was no potentiation of ACTH hypertension by ANG II in the sheep.

Adrenocorticotropic Hormone↗
PubMed1987

Structure-activity relationships for blood pressure effects of prednisolone in sheep.

This study investigated the effect of 5 day infusions of 6 alpha and 9 alpha-fluoro and 16 alpha, 17 alpha-acetal analogues of prednisolone on blood pressure in conscious sheep. In vivo mineralocorticoid (MC) and glucocorticoid (GC) activities of these steroids were also measured. Prednisolone (100 mg/d) produced a small increase in mean arterial pressure associated with increased fasting plasma [glucose] and polyuria, but had no MC activity. 9 alpha-fluoro substitution greatly enhanced both the pressor and MC activity of prednisolone. The effect of 9 alpha-fluoro substitution on pressor activity was not affected by beta-methylation at C-16 (betamethasone), but was attenuated by either alpha-hydroxylation or alpha-methylation at C-16 (triamcinolone and dexamethasone, respectively). The effect of 9 alpha-fluoro substitution on MC activity as determined by urinary Na excretion was not altered by a methyl group at C-16 in either alpha or beta configuration but the MC activity was attenuated by an alpha-hydroxyl group at C-16. In contrast, 6 alpha-fluoro substitution had little influence on pressor, MC and GC activities. 16 alpha, 17 alpha-acetonide and 16 alpha, 17 alpha-butylidenedioxy substitution increased the pressor activity of parent compounds, but had no influence on either GC or MC activity. This study demonstrates a dissociation between the pressor effects and the MC and GC activities associated with steroid administration and provides further evidence to support the concept of 'hypertensinogenic' class of steroid activity which can be distinguished from their MC and GC activity.

Animals↗
PubMed1987

On the brain involvement in saline loading natriuresis--an indirect evidence for the cerebral participation in the functional expression of the atrial natriuretic system.

The ablation of the anterior third cerebral ventricle region totally prevented the homeostatically effective natriuresis which should have followed hypertonic saline loading in conscious sheep. The increased cerebrospinal fluid (CSF) sodium concentration potentiated, and the decreased CSF[Na] prevented, natriuresis during isotonic saline loading. It is thus probable that a cerebral natriuretic system is involved in the functional expression of any other peripheral natriuretic system, e.g. the heart atrial natriuretic system which has been found to play a role in both hypertonic and isotonic saline loading natriuresis.

Animals↗
PubMed1987

Brain involvement in the regulation of renal sodium excretion.

The aim of the present work was to study some aspects of the brain involvement in renal sodium excretion from the point of view of renal regulation of the extracellular fluid volume and composition. It was found on the basis of experiments on conscious sheep that sodium concentration in the cerebrospinal fluid may be of importance for the mechanism of the extracellular fluid volume regulation. Higher concentrations potentiate a homeostatically effective natriuresis during extracellular fluid volume expansion and lower concentrations impair natriuresis. It was also found in sheep with lesions of the anterior third cerebral ventricle that this brain region is of crucial importance for the mechanism of natriuresis evoked by an i.v. hypertonic saline load but the regulation of the extracellular fluid volume is undisturbed provided the sheep is kept in water balance. Finally it was demonstrated in anesthetized dogs that the heart atrial natriuretic system may be under control of both the extracellular fluid volume and plasma osmolality (and/or plasma sodium concentration) and a circumstantial evidence was provided that it may also be under the control of a cerebral function.

Animals↗
PubMed1986

Augmented plasma renin levels in dehydrated sheep with periventricular lesions.

Ablation of tissue in the midline anterior wall of the third ventricle (AV3V) of sheep did not consistently alter baseline plasma renin concentration (PRC) in water replete animals, but caused a greatly augmented increase in PRC in response to water deprivation. PRC might increase in these sheep in order to maintain blood pressure, however it is possible that a central inhibitory influence on renal renin release, operative during dehydration, is disrupted by AV3V-lesions.

Animals↗
PubMed1986

Autoradiographic localization of angiotensin receptors in the sheep brain.

Binding of [125I]-(Sar1,Ile8)angiotensin II (AII) to frozen sections of sheep brain was determined by in vitro autoradiography. Greatest AII-binding occurred in the organum vasculosum of the lamina terminalis, subfornical organ, median preoptic and periventricular nuclei situated in the anterior third ventricle wall. Other binding sites included the hypothalamic supraoptic and paraventricular nuclei and the medullary nucleus tractus solitarius. These regions may be central receptor sites for AII involvement in fluid and electrolyte balance and blood pressure regulation.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1986

The effect of nivazol and cortivazol, novel synthetic steroids containing a phenylpyrazolo A-ring substitution, on blood pressure in sheep.

This study investigated the effect of 5 day infusions of two structurally novel synthetic steroids, nivazol and cortivazol on blood pressure and in vivo indices of "glucocorticoid" and "mineralocorticoid" activity. Cortivazol at 24 mg/day raised mean arterial pressure (MAP) by 16 mmHg (P less than 0.001). This was associated with increased cardiac rate, and increased fasting plasma [glucose], polyuria and polydipsia a trilogy characteristic of glucocorticoid effect. Cortivazol had no consistent action on plasma [Na] or [K], but caused an initial transient urinary Na retention and raised urinary excretion of Na and K on days 3 and 4 of treatment. Nivazol at 24 mg/day raised MAP 10 mmHg (P less than 0.001), but cardiac rate was unchanged. This infusion was also associated with the glucocorticoid effects of increased fasting plasma [glucose] and increased urine volume. Plasma [K] fell from a control of 4.4 +/- 0.1 to 4.0 +/- 0.1 mmol/l (P less than 0.01) after 5 days of infusion. There was no significant effect of nivazol on urinary Na or K excretion. This study demonstrates that replacement of the 3-keto group, by a bulky phenylpyrazolo group fused to the A ring at position 2 and 3, does not diminish either pressor or glucocorticoid activity of steroids containing the typical 4-pregnene-3,20-dione nucleus and confirms that the 3 keto group is not essential for optimal glucocorticoid activity. It is the first demonstration of the pressor effect of these novel steroids.

Animals↗
PubMed1986

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.

Animals↗
PubMed1986

The dipsogenic effect of intracerebroventricular infusion of hypertonic NaCl in the sheep is mediated mainly by the Na ion.

In order to examine the importance of the chloride ion in the dipsogenic effect of intracerebroventricular (ICV) infusion of hypertonic NaCl, the water intake in response to 30-min ICV infusions of hypertonic solutions of different Na salts (0.25 M NaCl, NaI, NaSCN and 0.125 M Na2S2O3), mannitol (0.5 M) and choline chloride (0.25 M) was studied in the sheep. All solutions of the Na salts caused significant water drinking compared with ICV control infusions of isotonic artificial cerebrospinal fluid (CSF), except Na thiosulphate (Na2S2O3), which was much less effective, even after equilibration of its osmolality with the other sodium solutions by adding mannitol (0.125 M Na2S2O3/0.25 M mannitol). An inconsistent and small intake of water was induced by ICV hypertonic mannitol and choline chloride. It is concluded that the dipsogenic effect of ICV infusion of hypertonic NaCl in the sheep is mainly caused by the increased Na rather than the Cl ion concentration or the hyperosmolality in the extracellular fluid of juxtaventricular brain tissue.

Animals↗
PubMed1986

Ablation of subfornical organ does not prevent angiotensin-induced water drinking in sheep.

The subfornical organ (SFO) and surrounding periventricular tissue were ablated in sheep. Such a lesion did not significantly reduce water drinking in response to intracarotid, intravenous, or intracerebroventricular infusions of [Val5]angiotensin II amide (ANG II) but caused reduced intake of water in response to intracarotid infusion of hypertonic saline. The dipsogenic response of these sheep to water deprivation for 3 days was similar to that of normal sheep subjected to water deprivation. Although the results are not conclusive in excluding the SFO from having a role in ANG II-induced drinking, they show that there are receptors outside the SFO sensitive to blood-borne ANG II that are involved in water drinking in sheep. The results also show that tissue in the SFO or its surroundings may be involved in drinking caused by acute hypertonicity.

Angiotensin II↗
PubMed1986

Volume influences on thirst and vasopressin secretion in dehydrated sheep.

The contribution of extracellular fluid volume (ECFV) to water consumption and plasma vasopressin concentration (PAVP) after water deprivation for 52 h was examined in sheep. Intravenous infusion of isotonic NaCl, equivalent to either estimated ECFV loss or total body water loss, significantly reduced water intake by 37% when water was offered 3 h after infusion but not when water was offered 1 h after infusion. Plasma osmolality (POsm) was reduced after 3 h. Infusion of 200 mM NaCl, which maintained POsm, decreased water consumption by the same degree as isotonic NaCl infusion. Thus large decreases in POsm had no effect on water intake in this experimental protocol. Lack of inhibition of drinking 1 h after infusion suggests that the decrease observed after 3 h may have been mediated by receptors in the interstitial fluid (ISF) compartment and not the intravascular compartment. PAVP was reduced 3 h after infusion of NaCl but not at 1 or 2 h after infusion. POsm was also decreased at 3 h. Thus reduction of PAVP by NaCl infusion may have been caused by either ISF or intracellular fluid volume expansion.

Animals↗
PubMed1986

Angiotensin and Na appetite of sheep.

The effect of both intravenous (iv; 24 micrograms/h) and intracerebroventricular (ivt; 3.8 micrograms/h) infusion over 1-2 days of angiotensin II (ANG II) on Na intake of both Na-replete and -deplete sheep (i.e., 22 h loss of parotid saliva) was observed. In Na-replete sheep with continuous access to water and 2-h daily access to 0.5 M NaCl solution, both iv and ivt ANG II caused an increase in Na intake. The increase in Na intake caused by iv or ivt ANG II was preceded by a Na deficit due to increased urinary Na excretion. The increase in Na intake was eliminated by the continuous return of urine. In Na-deplete sheep with continuous access to water and 2-h daily access to 0.6 M NaHCO3 solution, iv ANG II caused no change in Na loss but a small increase in Na intake during the 1st day of infusion. The ivt ANG II caused no change in Na loss or in Na intake. The iv ANG II caused a small and inconsistent increase in water intake in Na-replete sheep but did not cause any change in water intake of Na-deplete sheep. The ivt ANG II caused a large increase in water intake in both Na-replete and -deplete sheep. In both Na-replete and -deplete sheep, iv ANG II did not alter cerebrospinal fluid or plasma [Na] or osmolality but decreased plasma [K]. The ivt ANG II decreased both cerebrospinal fluid and plasma [Na] and osmolality. The results of the present experiments are consistent with the proposition that the ANG II-induced Na appetite in sheep is largely due to an ANG II-induced Na loss preceding the development of appetite.

Angiotensin II↗