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.

Atrial natriuretic factor and body water distribution.

In the rat, the effects of an atrial natriuretic factor (ANF) (Rat, 8-33 Peninsula Lab) on body water distribution have been evaluated. The ANF administration to nephrectomized animals produced a decrease in plasma volume and a slight increase in haematocrit and in plasma albumin concentration. No modifications were observed in total and intracellular water. The fluid efflux from the capillaries appeared to be located in the interstitial space. These results suggest that ANF could regulate plasma volume and systemic blood pressure, concurrently with its other known effects.

Baroreceptor mechanisms in rat.

Baroreflex control of cardiovascular parameters was studied in control, atropine- and guanethidine-treated rats. Baroreceptor activity was tested by the relationship between the increase in blood pressure produced by a phenylephrine administration (bolus ov infusion) and the induced bradycardia. No differences were observed in basal arterial blood pressure and heart rate between treated- and control rats. Baroreceptor sensitivity was lower in atropine- or guanethidine-treated rats than in control animals. Baroreceptor activity has two components: a first, rapid, predominantly parasympathetic and a second, slower, that is mediated by both parasympathetic and sympathetic efferent pathways.

Estimation of open-loop gain of rapidly acting arterial pressure control system in rats.

The overall open-loop gain of the rapidly acting arterial pressure control system was estimated in rats. Wistar male animals were bled by 6 ml/kg body weight. The open-loop gain of the rapidly acting arterial pressure control system was estimated as the relation between the fall of arterial pressure produced by the haemorrhage and the difference between control arterial pressure and the steady state reached after the recovery of the haemorrhage. The results observed suggest that the rapidly acting arterial pressure control system is less developed in the rat than in others Mammals.

Inhibition of water-sodium intestinal absorption by an atrial extract.

The rat atrium contains a diuretic and natriuretic factor which appears to inhibit the sodium reabsorption in the kidney tubules. We observed, in rats, that our atrial extract possesses a potent diuretic and natriuretic effect that was accompanied by an increased dextrose excretion. Similarly, extracts of rat atria, but not of ventricles, reduced intestinal absorption of water, sodium, and dextrose. The omission of sodium or dextrose in the perfusion fluid annulled this effect. These data suggest that the substance inhibiting the intestinal absorption of water and solutes is probably atrial natriuretic factor and that it acts on the sodium-dextrose cotransport mechanism.

Mechanism of urinary kallikrein excretion and its action on water excretion.

In male Wistar rats urinary kallikrein excretion was positively correlated with urinary flow and glomerular filtration rate and negatively with urinary osmolality and with TcH2O. The mechanism of urinary kallikrein excretion is interpreted as a wash-out effect of renal kallikrein. The renal kallikrein regulates the water excretion decreasing the reabsorption of water in the distal nephron.

Acute modifications of extracellular space components and urinary kallikrein excretion.

In control rats urinary kallikrein excretion was positively correlated with inulin space and its both components, plasma volume and interstitial space. When the animals were infused with dextrose solution or dextrose albumin solution the distribution of water in extracellular space was altered and the correlations with urinary kallikrein excretion disappear. We conclude that the possible regulation of the components of the extracellular space on urinary kallikrein excretion has not the same importance when water distribution is altered, at least in acute situations.

Effects of furosemide and captopril on submaxillary gland blood flow and arterial pressure.

The effects of furosemide and captopril were studied in nephrectomized rats with and without submaxillary gland. Captopril increased blood flow, but did not modified blood pressure. Furosemide plus captopril decreased significantly blood pressure. These results suggest a release of kallikrein by furosemide and probably a formation of kinin from plasma kininogen. On the other hand, rats sialodectomized showed no alterations in blood pressure in response to both drugs. These data suggest that submaxillary gland kallikrein participates in the mechanism of blood pressure regulation and blood flow of the gland at least in our experimental conditions. Glandular kallikreins are serine proteases which release kinins from substrates called kininogen. They are found in extracts and secretions of all exocrine glands. This proteases have been implicated in the regulation of exocrine glands and kidney blood flow, in water and electrolyte balance, in blood pressure regulation and in the pathogenesis of experimental and clinical hypertension (Carretero et al., 1978; Martinez Seeber et al., 1982). Glandular kallikreins of exocrine glands and kidney are secreted into the exocrine secretions and urine and also into the vascular compartment, where a local blood flow could be affected. According to Gautvik et al. (1980), rat submandibular gland is an organ rich in kallikrein, and significants amounts of the gland enzyme are release into the circulation after stimulation (Orstavik et al., 1982). Hilton and Lewis (1956) first proposed that glandular kallikrein-kinin system in salivary glands regulates vasodilation, probably through the effect of kallikrein on plasma kininogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of norepinephrine and vasopressin on renal kallikrein excretion in rats.

The purpose of this study was to investigate the effect of norepinephrine and vasopressin on urinary kallikrein excretion in the rat. Two studies were undertaken: (a) acute experiments in which the rats were infused with 30% dextrose in water with the addition of norepinephrine or vasopressin, (b) chronic experiments in which the drugs were infused during seven days through an osmotic minipump. In acute experiments, urinary kallikrein excretion increased without modification in urinary flow and glomerular filtration rate. In chronic experiments, urinary kallikrein excretion was not modified in norepinephrine-treated rats and decreased in vasopressin-infused animals. This decrease followed the modifications of the urine flow. In chronic experiments the dextrose infusion increased urinary kallikrein excretion. In all the groups studied a positive correlation between urine flow and urinary kallikrein excretion was observed. It is concluded that norepinephrine and vasopressin are important stimulators of the urinary kallikrein excretion only in those circumstances where it is necessary to eliminate an excess of water.

Effect of extracellular space on kallikrein excretion in the rat.

Urinary kallikrein excretion was positively correlated with urine flow and negatively with urinary osmolality, it was also positively correlated with inulin space and its both components, plasma volume and interstitial space. We postulate that increased extracellular fluid increases kallikrein excretion and kallikrein avoids water reabsorption leading to a decrease in the extracellular fluid.

Role of autonomic nervous system on heart rate in experimental hypertension.

Heart rate and the role of the autonomic nervous system in hypertensive conscious rats by subtotal nephrectomy were studied. Heart rate is significantly higher in the hypertensive rats. Sympathetic blockade with an intravenous injection of propranolol produces a higher decrease in heart rate of hypertensive rats than in control rats. Intravenous injection of atropine produces an increase in heart rate in both groups of animals. It is significantly higher in the control rats than in hypertensive animals. When the autonomic nervous system is blocked with atropine and propranolol, intrinsic heart rate is similar in both groups of animals. Similar results are obtained after blocking ganglionic transmission with hexamethonium. No significative differences are observed in heart rate after intracerebroventricular injection of hemicholinium-3 between both groups of rats. Results show an increased cardiac sympathetic tone, reduced parasympathetic activities, no alterations in the pacemaker activity and implications of central acetylcholine. These alterations in the autonomic nervous system have an important role in the maintenance of elevated heart rate in this experimental model of arterial hypertension.

Mechanism of urinary kallikrein excretion.

Urinary kallikrein excretion was compared with urea excretion in the rat and the results showed that they were correlated. Like urea excretion is flow-dependent, we conclude that the principal mechanism regulating kallikrein excretion is a wash-out effect on renal kallikrein.

Effect of angiotensin, noradrenaline, vasopressin and aldosterone on urinary kallikrein excretion in the rat.

In male Wistar rats, under osmotic diuresis, the effect of angiotensin II, noradrenaline, vasopressin and aldosterone on urinary kallikrein excretion were evaluated. Angiotensin II did not modify but all the others drugs used increased significantly the urinary kallikrein excretion. In all the groups studied the urinary sodium excretion increased. No modifications were observed in urine flow, glomerular filtration rate, urine osmolality and potassium excretion. The urinary kallikrein excretion was always positively correlated with the urinary flow and urinary sodium excretion. No correlation was observed with the other parameters studied. These findings suggest that noradrenaline, vasopressin and aldosterone are important stimulators of the urinary kallikrein excretion. Probably, kallikrein is one of the mechanisms involved in the regulation of urinary sodium excretion.

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.

Kallikrein and amylase contents in tissues from a mutant mouse model for human cystic fibrosis.

Kallikrein and amylase activities are decreased in the pancreas and salivary glands from cri/cri homozygote mutant mice. Kallikrein is decreased in the cri/cri kidney too. With reference to nucleic acid concentrations there is no difference between control and mutant mice. The previously described electrolyte abnormalities of the cribriform degeneration (cri) mutant mouse, could be due to the abnormal activity of the kallikrein-kinin system on the transport mechanism of tubular cells in the organs mentioned. These findings represent a new step on our efforts to develop a useful animal model for human cystic fibrosis research.

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).

The mechanism of urinary kallikrein excretion in the rat.

1. In male Wistar rats urinary kallikrein excretion was positively correlated with urinary flow and glomerular filtration rate (GFR). 2. Osmotic diuresis produced by a 30% (w/v) glucose solution increased urinary kallikrein, and a positive correlation between this variable and urine flow was observed. No correlation was observed with GFR. 3. The mechanism of urinary kallikrein excretion is interpreted as a wash-out effect of renal kallikrein.

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.