Quantitative modifications induced by angiotensin II on rat bile secretion.

Angiotensin II (ANG II) effects on bile secretion were studied in the rat. ANG II (0.1 microgram/kg) was injected into the jugular vein every 30 min and bile samples of 30 min were collected for 120 min. Blood arterial and portal venous pressures were simultaneously recorded before and after the administration of ANG II. Results showed that ANG II decreased bile flow and the excretion of sodium, potassium, chloride and bile acids whereas it increased pH, bile osmolality and the excretion rate of bicarbonate and calcium. ANG II also led to a rapid increase in mean arterial pressure as well as portal venous pressure which reverted to control values within 1 min. The present results suggest that ANG II may modulate bile flow and the excretion rate of the different biliary constituents. We have previously investigated atrial natriuretic factor effects on bile secretion and although the atrial factor antagonizes most of ANG II biological actions, unexpectedly, ANG II effects on bile secretion were not opposite to those of atrial natriuretic peptide. The modifications induced by ANG II on bile secretion may play an important role in pathophysiological conditions such as hypertensive states with increased ANG II circulating levels.

Atrial natriuretic factor modifies bile flow and composition in the rat.

The effects of atrial natriuretic factor (ANF) on bile secretion were studied in the rat. ANF was injected 'in bolus' (5.0 micrograms/kg) every 30 min into the jugular vein. The common bile duct was cannulated and bile samples were collected every 30 min for 120 min. Systemic blood arterial pressure was registered before and after the administration of ANF. Results showed that ANF decreased bile flow and the excretion rate of sodium, potassium, chloride, bile acids, cholesterol and proteins. On the other hand, it increased pH and the excretion of bicarbonate and calcium. As ANF slightly reduces mean arterial pressure, its vascular effect may not be considered the major event. In addition, increased excretion of bicarbonate and calcium, and the fact that ANF vascular effect is short in time suggest that the peptide may have a non-vascular effect on the processes of bile formation and its modifications along the bile ducts. This extravascular effect may be exerted on the hepatocyte ions exchangers and/or at the ductal level on the processes of excretion and reabsorption of electrolytes and water.

Role of atrial natriuretic peptide on calcium channel mechanisms involved in catecholamine release from bovine adrenal medulla.

The role of the atrial natriuretic peptide on calcium channel mechanisms involved in catecholamine release was studied in the perfused bovine adrenal medulla. The atrial natriuretic peptide (1 nM and 10 nM) did not modify the spontaneous release of catecholamines. Ten nM of atrial natriuretic peptide decreased the output of catecholamines induced by acetylcholine, KCl-depolarizing solutions and angiotensin II. It was ineffective to modify the catecholamine release when calcium channels were blocked or in the presence of calcium-free media. Moreover, the deprivation of the ion calcium in the media decreased the catecholamine release induced by KCl to a lowest level, despite the presence of atrial natriuretic peptide in the perfusate. In conclusion, atrial natriuretic peptide inhibited the induced secretion of catecholamines in the bovine adrenal medulla and interfered as a partial blocker with calcium-dependent mechanisms.

Angiotensin II increases MAO activity in rat central nervous system.

The effects of angiotensin II (ANG II) and bilateral nephrectomy on monoamine oxidase (MAO) activity were studied in rat hypothalamus and medulla oblongata. ANG II increased MAO activity in both central nervous system (CNS) regions. The fall of circulating ANG II caused by 48 h bilateral nephrectomy decreased the activity of the enzyme in the mentioned areas. The results showed that ANG II stimulates catecholamine metabolism in the CNS.

Effects of angiotensin II and bilateral nephrectomy on norepinephrine catabolism in central nervous system.

Effects of angiotensin II (AII) on norepinephrine (NE) catabolism in hypothalamus and medulla oblongata of male rats were studied. 3H-NE uptake, 3H-NE/3H-NE metabolites ratio (NE/MET) and monoamineoxidase (MAO) activity were measured in vitro in both organs. Lack of circulating AII was elicited by means of 48 h bilateral nephrectomy. Pargyline and bilateral nephrectomy increased NE uptake and NE/MET ratio, while in nephrectomized plus pargyline treated groups and additive effect on these results was observed in both organs. All decreased the NE/MET ratio. Pargyline reversed the latter effects of AII. The peptide increased MAO activity in both organs, while bilateral nephrectomy decreased the activity of the enzyme. The results showed that AII modulates NE catabolism by means of MAO activity, eventually at the presynaptic noradrenergic ending sites in the central nervous system.

Atrial natriuretic peptide and angiotensin II interaction on noradrenaline uptake in the central nervous system.

The effects of different concentrations of atrial natriuretic peptide and angiotensin II on [3H]-noradrenaline uptake in hypothalamus and medulla oblongata slices incubated in vitro were determined. Atrial natriuretic peptide, in a dose of 100 mM, increased [3H]-noradrenaline uptake in both regions, while 1 microM of angiotensin II had the opposite effect. The ineffective concentration of 1 nM atrial natriuretic peptide reversed the action of 1 microM of angiotensin II on [3H]-noradrenaline uptake, whereas ineffective concentrations of angiotensin II failed to modify atrial natriuretic peptide effects. These results are compatible with the existence of an atrial natriuretic peptide-angiotensin II interaction in the central nervous system and with the hypothesis that some of the hypotensive effects of atrial natriuretic peptide could occur through modulation of an angiotensin-noradrenergic mechanism in the central nervous system.

Different inhibitory sites of action for magnesium and verapamil in the bovine adrenal medulla.

The effects of verapamil and Mg2+ on catecholamine release induced by the substitution of NaCl by sucrose in the extracellular medium were studied in the perfused bovine adrenal medulla. Verapamil (3 X 10(-4) M) totally blocked the acetylcholine-evoked release of amines, but failed to antagonize the secretory response promoted by NaCl-omission. Perfusing glands with a Locke solution containing 10 mM Mg2+, produced a 61.4 and 62.8% inhibition of catecholamine release induced by acetylcholine and by NaCl-deprivation respectively. A similar inhibitory effect of Mg2+ (10-20 mM) was obtained in glands exposed to a NaCl-free solution in the absence of extracellular Ca2+. In adrenal glands previously perfused with verapamil (3 X 10(-4) M) and then exposed to a Locke solution containing verapamil (3 X 10(-4) M) and Mg2+ (10 or 20 mM) the inhibition of the secretory responses promoted by NaCl-omission was of the same magnitude as that obtained when the glands were perfused with Mg2+ (10 or 20 mM) in the absence of verapamil. A similar lacking effect of verapamil on the blocking action of Mg2+ on catecholamine release evoked by NaCl-deprivation was observed in the absence of extracellular Ca2+. These results are compatible with the idea that in the bovine adrenal medulla verapamil and Mg2+ could have different inhibitory sites of action. Verapamil would exert its blocking effect at an extracellular site, while the inhibitory action of Mg2+ may be mediated by an intracellular site. An additional extracellular locus of action for Mg2+ at the external surface of the chromaffin cell cannot be discarded. These results also suggest that calcium channels may not be involved in the inward transport mechanism of Mg2+ to its intracellular locus of action.

Predictability of serum digoxin concentrations in clinical practice.

A study was conducted to clarify the reliability of serum digoxin concentration (SDC) predictions in the absence of concurrent quinidine administration. The effects of age, sex, congestive heart failure (CHF), and the method used to estimate creatinine clearance were investigated. Data were collected from patients who were representative of those seen in clinical practice. Patients admitted to the study were required to have not received quinidine, to have stable renal function, to have been taking digoxin for ten consecutive days--the same dose and route of administration, and to have been categorized as having or not having CHF at the time of the SDC determination. There were 44 patients who qualified for admission to the study. SDCs were predicted on the basis of four methods for estimating creatinine clearance and four methods for estimating serum concentrations. After simple linear regression analysis, one method was found to have correlation coefficients ranging from 0.72 to 0.79, regardless of the method used to estimate creatinine clearance. In addition, analysis determined that age and presence of CHF were not factors affecting the reliability of predicted SDCs. Female patients had, on the average, a greater difference between measured and predicted SDCs; however, this was not statistically significant. Thus, in the absence of concurrent quinidine administration, SDCs may be estimated as long as the limitations of the method are acknowledged. Age, CHF, and the common methods used to estimate creatinine clearance do not significantly affect the reliability of predicted SDC values.

[The renin-angiotensin system and noradrenaline release in the hypothalamus and medulla oblongata]. / Sistema renina-angiotensina y liberación de noradrenalina en el hipotálamo y bulbo raquídeo.

The effect of angiotensin II (AII) and 48 h bilateral nephrectomy on the 3H-norepinephrine (3H-NE) and 3H-NE metabolites release in vitro was studied in slices of male Wistar rat hypothalamus and medulla oblongata. The total 3H outflow of radioactivity was higher in AII exposed tissues than in nephrectomized ones of both organs. The 3H-NE and 3H-NE metabolites remanent radioactivity in the tissues increased in both the soluble cytoplasmatic fractions and the granular vesicle ones, in the two organs from the nephrectomized rats. The ratio between granular and cytoplasmatic NE and granular and cytoplasmatic radioactive metabolites was not noticeably altered in any of the groups. The release of 3H-NE caused by AII and the opposite effect by nephrectomy, agree with the inverse relationship demonstrated between endogenous NE content in the central nervous system and AII plasmatic levels. AII might act on presynaptic NE receptors of the cellular membrane. The relationship between the renin-AII system and the central nervous system catecholamines could be involved in the control of development and maintenance of the renal arterial hypertension.

Contrasting effect of verapamil on catecholamine release induced by acetylcholine and by NaCl-omission from the bovine adrenal medulla.

Verapamil (3 X 10(-4) M) produced a 92.2% inhibition on the release of catecholamines induced by acetylcholine in perfused bovine adrenal glands. This blocking effect was slowly reversible. On the other hand, verapamil (3 X 10(-4) M) failed to antagonize the secretory response evoked by the substitution of NaCl by sucrose in the perfusion fluid. A similar lack of inhibitory effect of verapamil on catecholamine output produced by NaCl-omission was observed in the absence of extra-cellular Ca2+. These results suggest that Ca2+ influx might not be involved in adreno-medullary secretion induced by the substitution of NaCl by sucrose in the perfusion medium.

Angiotensin II-norepinephrine relationship in the central nervous system.

The effects of angiotensin II (AII) and bilateral nephrectomy on [3H] norepinephrine (NE) uptake in hypothalamus and medulla oblongata were studied in male rats. The endogenous NE content in hypothalamus increased 4, 24 and 48 h after nephrectomy with a simultaneous decreasing of plasma renin activity. Intraventricularly infused [3H] NE uptake increased in hypothalamus and medulla oblongata of nephrectomized animals in cytoplasmatic compartment as in granular stores, while it decreased in hypothalamus of AII-infused animals. [3H] NE metabolites radioactivity decreased in nephrectomized animals if they are compared with AII-infused ones. These changes were independent of systolic arterial pressure that was not modified in none of the groups. The study of the ratio granular/cytoplasmatic [3H] NE and metabolites radioactivity shows that AII probably acts on cellular membrane uptake of NE. The modification of metabolites/NE ratio in both stores would be due to AII action on MAO activity. The effects of AII and nephrectomy on [3H] NE uptake can explain the inverse relationship between circulating AII levels and NE content in the central nervous system (CNS).

Characteristics of the arterial hypertension by subtotal nephrectomy in the rat.

The importance of the hemodynamic parameters in the hypertensive rats by subtotal nephrectomy and the role of the neurogenic tone in the maintenance of high blood pressure were studied. The baroreceptor sensitivity is significantly diminished in the hypertensive rats with respect to normal ones. The resistance of the hindquarters to perfusion with constant flows was decreased in the hypertensive animals. No differences were observed in the arterial pressure, cardiac output, heart rate, stroke volume and peripheral resistance between both groups of anesthetized animals. The pressure response to the phenylephrine injection was higher in the conscious hypertensive animals than in the normotensive rats but it was the same after the anesthesia and the blocking of ganglionic transmission. These results suggest that an increment of the neurogenic tone exists in the chronic phase of hypertension in this experimental model and it could be responsible for the elevated blood pressure.

Saralasin and SQ 20881 : their effects on central nervous system norepinephrine.

The effects of the infusion of Saralasin and SQ 20881, two drugs that inhibit the renin-angiotensin system, on the norepinephrine (NE) concentration in hypothalamus and medulla oblongata were studied in male Wistar rats. NE content increased in hypothalamus in response to both drugs, without changes in medulla oblongata catecholamine concentration. These results showed that the NE concentration of certain areas of the central nervous system can be modified, in a short time, by the inhibition of the renin-angiotensin system. Results observed after the infusion of Saralasin could indicate that the receptors, on which the angiotensin acts to produce this alteration, are similar to those of the peripheral blood vessels.

[Relation between urinary catecholamine and gonadotrophins and sexual hormones (author's transl)]. / Relación de las catecolaminas urinarias con las gonadotrofinas y las hormonas sexuales.

The urinary excretion of the norepinephrine, epinephrine and the norepinephrine/epinephrine ratio and its modifications by the ovariectomy, adrenalectomy, hypophysectomy and the administration of sexual hormones and gonadotrophins were studied in female Wistar rats. The ovariectomy increased epinephrine excretion and decreased the studied ratio. The adrenalectomy increased norepinephrine and the ratio levels and diminshed epinephrine excretion. Norepinephrine and norepinephrine/epinephrine ratio elimination increased in the ovariectomized and adrenalectomized rats. The sexual hormones did not alter catecholamine levels in the ovariectomized and adrenalectomized animals and were not effective to restore the control levels. The norepinephrine/epinephrine ratio reached a maximum under progesterone effects. Both urinary catecholamines rose in ovariectomized and hypophysectomized animals. The chorionic and the equine gonadotrophins did not restore the control levels, but they had a tendency to do it. The results showed the existence of a close interelationship between the sympathetic system and the sexual hormones and gonadrotrophins function, that could be related to regulatory mechanisms of the hypophyseal gonadotrophins secretion.

Modifications of arterial pressure and plasma renin: their effects on the norepinephrine content of hypothalamus and medulla oblongata.

The effects of the bilateral nephrectomy and acute hypotension caused by the cava vein ligature on the norepinephrine (NE) concentration in hypothalamus and medulla oblongata and on the plasma renin activity were studied in male rats. NE increased and plasma renin activity decreased in hypothalamus in 24 h nephrectomized rats with or without the ligatures of the cava vein. NE also decreased in medulla of groups with the ligatures only. The mean arterial pressure, did not correlate with the NE or plasma renin activity levels. The modifications of the NE in the central nervous system showed an inverse relationship with plasma renin activity and this, could be due to changes in the NE uptake and/or release caused by the plasma renin activity alterations. NE modifications do not seem to be caused directly through reflex of the arterial pressure.