The role of the autonomic nervous system in the depression of parotid salivary secretion during hyperkalaemia in conscious sheep.

The rate of flow and electrolyte concentration of parotid saliva were measured before, during and after intravenous and contralateral intracarotid infusion of KCl (0.5 mol.1(-1)) and NaCl (0.5 mol.1(-1)) at 385-625 mumol. min(-1) for 40 min into 5 sheep. In intact conscious sheep contralateral intracarotid infusion of KCl caused marked depression of salivary secretion in all experiments whereas infusion of NaCl had no consistent effect on flow. Intravenous infusion of KCl into the intact conscious sheep caused a slight depression of salivary secretion but minimum flow was significantly higher than that during intracarotid infusion. When the sheep were anaesthetized salivary flow rates were low and contralateral intracarotid infusion of KCl either had no effect on flow or caused an increase in flow. After ipsilateral cervical sympathectomy contralateral intracarotid infusion of KCl into the conscious sheep caused a marked depression of salivary flow similar to that occurring when the sheep were intact. After section of the secretomotor nerve of the gland salivary flow rates were low and contralateral intracarotid infusion of KC1 had no effect on flow. The salivary flow responses of the sheep were consistent, regardless of whether the KCl infusions were given within 24 h or 1-2 weeks after cervical sympathectomy or secretomotor nerve section. Salivary sodium concentration was negatively correlated with salivary flow in all experiments. It was concluded that potassium acted at a site located in the head but by direct action on the salivary gland. The depression of salivary secretion by hyperkalaemia resulted from a decline in neural activity in the parasympathetic secretomotor innervation of the parotid gland.     

Changes in arterial blood pressure, heart rate and haematocrit during acute hyperkalaemia in conscious sheep.

The systolic, diastolic and mean arterial blood pressures, heart rate and haematocrit were measured at 15 minute intervals before, during and after 2 hour infusions of 0-4 mol.l-1 NaCl at 2-2 ml min-1 into conscious intact sheep and 0-4 mol. l-1 KCl at 2-2 ml. min-1 into conscious sheep which were either intact or adrenalectomized. The haemotocrit was also measured in splenectomized sheep receiving 0-4 mol. l-1 KCl. The NaCl infusion had no significant effect on blood pressure(BP), heart rate and haematocrit. Both intact and adrenalectomized sheep were able to withstand an increase in plasma potassium concentration in excess of 50% of the preinfusion concentration before any substantial fall in BP occurred. In intact and adrenalectomized sheep, heart rate and haematocrit increased rapidly and progressively throughout the potassium infusions and at maximum plasma potassium concentration the mean increments in these parameters for both groups of sheep were 21-6+/-2-69 beats/min and 7-5+/-0-47% respectively. Heart rate and haematocrit were more closely correlated with the plasma potassium concentration than with any other variable measured in these experiments. Adrenalectomy did not reduce the ability of the sheep to maintain their BP or to increase their heart rate and haematocrit. As the mean increase in haematocrit during potassium infusion into splenectomized sheep was 1-3+/-0-45% most of the increase in haematocrit observed in the potassium-infused intact and adrenalectomized sheep was caused by ejection of red cells from the spleen into the circulation.     

Plasma insulin concentrations during infusions of potassium and sodium chloride solutions into conscious splenectomized sheep

Haematocrit values, plasma osmolality and the plasma concentrations of sodium, potassium, chloride and insulin were measured in carotid arterial blood before, during and after intravenous infusion of NaCl (0.5 mol 1-1) and KCl (0.5 mol 1-1) at 2 ml min-1 for 105 min into six conscious splenectomized sheep. Hypertonic NaCl infusion was associated with a fall in haematocrit of 1.30 +/- 0.10% (P less than 0.001) and no consistent change in plasma insulin concentration occurred during this infusion. Hypertonic KCl infusion caused the haematocrit to increase by 1.70 +/- 0.39% (P less than 0.001) and the plasma insulin concentration to increase by 60.0 +/- 16.3 mu U ml-1 (P less than 0.01). It was concluded that this increase in insulin concentration was caused by elevation of the plasma potassium concentration and was not due to coincident increases in plasma chloride concentration or osmolality. Shrinkage of the extracellular fluid volume during KCl infusion made no major contribution to the increase in insulin concentration which was probably the result of increased release from the pancreas.     

Changes in urinary water and electrolyte excretion in sodium-loaded sheep in response to intravenous infusion of arginine vasopressin.

Mature sheep receiving supplements of sodium chloride into the rumen were given intravenous infusions of arginine vasopressin at rates varying from 4-6-23 pmol/min (2-10 mU/min). Infusion of the hormone led to an increase in urine flow and to increases in the amounts of sodium and chloride excreted, the effect on flow was, however, the greater so that the osmolality of the urine fell during the infusions. In sheep given intravenous infusions of a hypertonic sodium chloride solution addition of vasopressin to the infusate led to the formation of a larger volume of urine containing a higher proportion of the infused salt load compared to when the salt solution alone was given. As before the effect on flow was the greater and hence the osmolality of the urine was lower when the hormone was given. In other experiments intravenous infusion of a hypertonic sodium chloride solution at rates providing 2-8 mmol NaCl/min led to increases in urine flow and increases in sodium and chloride excretion, the size of these increases being proportional to infusion rate. Plasma vasopressin levels markedly increased during these infusions, the levels seen being similar to those seen in sheep given vasopressin in amounts which increased both urine flow and electrolyte excretion. This suggests that during hypertonic salt loading vasopressin probably contributes directly to the increases in urine flow and the increases in electrolyte excretion which are seen. Further evidence in support of this was obtained in experiments in which a greater natriuretic response was seen in sheep given a hypertonic sodium chloride solution into the carotid artery as opposed to the given a hypertonic sodium chloride solution into the carotid artery as opposed to the jugular vein and where it was shown that plasma vasopressin levels were indeed higher when the solution was given into the artery.     

The composition and flow of parotid saliva during acute hyperkalaemia in sodium-deficient sheep.

Sheep were infused intravenously with 0-43 M-KCl at 2 ml/min for 2 hr while they were either sodium-replete or sodium-deficient after the unilateral loss of parotid saliva for 18 hr or 3 days. Salivary flow was depressed during potassium infusion and the flow rates observed at maximum hyperkalaemia were similar in all three states of sodium balance despite the large differences in flow rate before potassium infusion. The fall in salivary Na/K ratio during potassium administration was diphasic, the initial decline being slow and followed by a more rapid fall in the ratio. The duration of the initial period of slow decline in this ratio ranged from 75-105 min, 45-60 min, and about 15 min in the sodium-replete, mildly sodium-deficient and severely sodium-deficient states respectively. The decline in salivary flow during sodium depletion was associated with decreasing salivary bicarbonate concentration and increasing salivary phosphate and hydrogen ion concentrations with the concentration of chloride showing no consistent trend. During acute hyperkalaemia the chloride and phosphate concentrations were negatively correlated with salivary flow, the bicarbonate concentration was positively correlated with flow and the hydrogen ion concentration was unaltered. The sodium concentration of the saliva showed a statistically significant correlation with flow only when the sheep were severely sodium-deficient.     

The effects of two analogues of arginine-vasopressin (ornithine-vasopressin and desamino-D-arginine-vasopressin) on kidney function in sheep.

The effects of intravenous infusion of ornithine-vasopressin (OVP) and desamino-D-arginine-vasopressin (dDAVP) were studied in normal and hydrated Merino sheep. In normal sheep, OVP resulted in a diuresis, increased urinary sodium and potassium excretion, and a fall in the plasma potassium concentration. Renal plasma flow remained constant but glomerular filtration rate and filtration fraction rose markedly. dDAVP in normal sheep was antidiuretic, but its only significant effect was a small decrease in plasma osmolality. In the hydrated sheep OVP was antidiuretic and resulted in increased urinary excretion of sodium and potassium, and a fall in the plasma potassium level. Renal plasma flow fell, but glomerular filtration and filtration fraction tended to rise. dDAVP in the hydrated sheep was also antidiuretic but urinary sodium and potassium excretion was reduced. Renal plasma flow and glomerular filtration fell, with a small decrease in filtration fraction. These results suggest that the diuretic effect in normal sheep and the electrolyte-excreting effects in both normal and hydrated sheep of OVP are related to the increase in glomerular filtration, which in turn is dependent on the vasopressor activity of the hormone. The increase in glomerular filtration caused by OVP is due to an increase in the filtration fraction of an unchanged renal plasma flow, which could be brought about by an increase in renal efferent arteriolar tone. The effects of hydration of the sheep were the conventional increased urine flow, decreased urine osmolality and decreased solute-free water reabsorption. Sodium and potassium excretion rose slightly and plasma osmolality fell. Renal plasma flow and glomerular filtration both increased with little change in filtration fraction. These effects could be brought about by suppression of endogenous vasopressin and a decrease in both afferent and efferent renal arteriolar tone.     

The effects of intracerebroventricular infusion of atrial natriuretic factor in conscious sheep

The effects of 24-hour intracerebroventricular infusion of human atrial natriuretic factor (ANF) and two related fragments were studied in conscious sheep. ANF (1-28) had no effect on either mean arterial pressure (MAP) or heart rate (HR) when infused at 3 or 10 micrograms/hr, however a small diuresis and an increase in urinary sodium (Na) excretion was observed. The smaller fragment, ANF (5-27) infused at 10 micrograms/hr, increased MAP, HR and body temperature, although the same rate of infusion of ANF (5-28) was without effect. All peptides increased plasma sodium concentration and plasma osmolality. None of the peptides affected plasma ACTH, glucose or renin concentration. ANF (1-28) had no effect on either Na intake or water intake in Na-depleted sheep. These studies suggest that members of the ANF family can influence a number of physiological functions following central administration.     

Diuretic effect of intraventricular and intravenous infusions of noradrenaline in conscious sheep

Infusion of noradrenaline at rates between 32-160 nmol.min-1 for 30 min into one lateral cerebral ventricle of conscious sheep caused a diuresis which was accompanied by negative solute-free water reabsorption and which lasted for 90-120 min. The range of noradrenaline infusion rates used reflects differences between individual animals in the rate of infusion necessry to cause diuresis. Intracerebroventricular (ICV) infusion of noradrenaline at half the diuretic rate caused no significant changes in urine flow. The diuresis induced by ICV noradrenaline infusion was prevented by concurrent ICV administration of the alpha-adrenergic antagonist, phentolamine, but was not prevented by concurrent ICV administration of the beta antagonist, propranolol, or by concurrent intravenous infusion of phentolamine. Intravenous infusion of noradrenaline at rates that were diuretic by ICV infusion caused a diuresis of approximately 30 min duration which coincided with the period of intravenous noradrenaline infusion. This diuresis was prevented by concurrent intravenous infusion of phentolamine. These results were interpreted as indicating that the higher rates of ICV infusion of noradrenaline caused the prolonged water diuresis by acting at a site in the brain and, thereby, inhibiting the release of endogenous vasopressin. ICV infusion of noradrenaline at all rates was followed by a reduction in mean arterial blood pressure and pulse pressure with variable changes in heart rate and by depression of the rates of renal clearance of PAH, potassium and total solute.     

Influence of insulin on plasma concentration and renal excretion of sodium and potassium in normal, electrolytes depleted and aldosterone treated dogs

Effects of insulin on plasma concentration and renal excretion of sodium and potassium were compared in conscious dogs 1) maintained in water and electrolytes balance (Series 1, 10 dogs), 2) depleted of electrolytes by repeated i.v. loading with 20% mannitol (Series 2, 10 dogs), and 3) aldosterone treated (0.8 micrograms.kg-1.h-1 i.v., Series 3, 10 dogs). In each Series intravenous infusion of insulin at a rate of 0.05 U.kg-1.h-1 elicited transient increase in plasma sodium concentration and prolonged hypokalemia. Repeated loading with mannitol in Series 2 elicited significant elevation of plasma sodium, ADH and aldosterone concentrations, as well as decrease in extracellular fluid volume. Infusion of insulin in this Series elicited smaller decrease in plasma potassium concentration and longer lasting hypernatremia than in dogs in water-electrolytes balance. Aldosterone infusion in Series 3 did not change hypokalemic effect of insulin but attenuated hypernatremia. Infusion of insulin in Series 1 elicited increase of sodium excretion and decrease in potassium excretion. These effects were absent in Series 2 and 3. The results indicate that depletion of electrolytes and blood aldosterone elevation modify the effects of insulin on plasma concentration and renal excretion of sodium and potassium.     

Renal function and plasma arginine vasotocin during an acute salt load in feral chickens

Summary Renal clearance experiments were conducted on feral chickens descended from birds collected from a coral island off the coast of Queensland, Australia. Following a control period when 0.13 M NaCl was used as a vehicle for the renal function markers, a salt load was imposed by infusion of 1 M NaCl. The hypertonic NaCl infusion resulted in increases in glomerular filtration rate (GFR), effective renal blood flow (ERBF), and urine flow rate (V), whereas filtration fraction decreased. Haematocrit was reduced and plasma osmolality, sodium, chloride and potassium concentrations increased. Plasma arginine vasotocin (P_AVT) levels increased from 31.4±2.3 pg·ml^-1 during the control infusion to 56.0±1.7 pg·ml^-1 following a salt load of 12 mmol Nacl·kg^-1 The sensitivity of release of AVT was 0.69±0.11 pg·ml^-1 per mosmol·kg^-1. The concentrations of Na and Cl in urine increased, whereas urine osmolality and potassium concentration decreased. The expansion of the extracellular fluid volume induced by the salt loading would tend to suppress the release of AVT, whereas the osmotic stimulus would provide a stimulus for the release of AVT. In this study, GFR, ERBF and ERPF increased at the same time as P_AVT increased.Abbreviations AVP arginine vasopressin - AVT arginine vasotocin - ERBF effective renal blood flow - ERPF effective renal plasma flow - GFR glomerular filtration rate - P_avt plasma arginine vasotocin concentration - PAH paraaminohippuric acid - SEM standard error of mean - SNGER single nephron glomerular filtration rate - U/P urine to plasma ratio - V urine flow rate     

The effects of vasopressin on renal sodium excretion in pigs given intravascular hypertonic salt loads

Young pigs of about 25-30 kg liveweight were given intravenous infusions of a hypertonic sodium chloride solution (4-6 mol.1(-1)) at rates varying from 2-6 mmol.min-1. Such infusions resulted in a marked increase in the urine flow and in urinary sodium excretion, the size of these increases being proportional to infusion rate. Circulating vasopressin levels were also markedly increased, the size of these increases being the same as those seen in other pigs given exogenous vasopressin in amounts which were shown to increase urinary sodium excretion. This suggests that vasopressin was probably contributing to the increase in renal sodium excretion seen in those pigs given the intravenous salt loads.     

The effects of handling procedures,breed differences and treatment with lithium and dexamethasone on some blood parameters in sheep

Fifteen aged Merino and 15 aged Border Leicester ewes each divided into 3 groups of 5 for infusion with lithium chloride, lithium chloride plus dexamethasone and normal saline, and then subjected to 3 jugular venous blood samplings, 1 h apart, in a 3 × 3 × 2 experimental design involving times × treatments × breeds.The blood samples were examined for packed cell volumes, plasma and erythrocyte sodium and potassium concentrations, and plasma calcium concentrations.There were significant changes in packed cell volumes (PCV) 39 v. 30%; 39 v. 31%), plasma sodium concentrations (151 v. 149 mmol l⁻¹; 151 v. 148 mmol l⁻¹) and plasma potassium concentrations (5.3 v. 4.6 mmol l⁻¹; 5.3 v. 4.7 mmol l⁻¹) between Times 0 and 1 and between Times 0 and 2, respectively. There were no significant changes in plasma calcium or erythrocyte sodium or potassium concentrations associated with times. The evidence suggests that the times-effects were caused by different methods of handling the sheep immediately prior to each blood sampling, and this is discussed. The fall in PCV was greater than that recorded by other authors.There were highly significant (P < 0.01) breed differences in PCV (36 v. 31%), plasma calcium concentrations (2.0 v. 2.2 mmol l⁻¹) and erythrocyte potassium concentrations (10.1 v. 15.0 mmol l⁻¹) for Merino and Border Leicester ewes, respectively. There were no significant breed differences in plasma potassium or erythrocyte sodium concentrations.The mean plasma potassium concentration of 5.08 mmol l⁻¹ for the lithium-treated sheep was significantly higher than the means of 4.67 and 4.77 mmol l⁻¹ for lithium plus dexamethasone and saline-treated groups, respectively. There was no significant difference between the latter two means, and there were no significant treatment effects for any of the other blood constituents.     

Urinary selenium excretion in selenite-loaded sheep and subsequent Se dynamics in blood constituents

Renal selenium excretion in sheep was measured during intravenous infusion of sodium selenite, and the post-infusion dynamics of Se levels in whole blood, plasma and red blood cells (RBC) were investigated for the next 5 days. The plasma Se level increased almost twenty fold with the infusion of Na2SeO3 (from 0.39 +/- 0.02 to 7.83 +/- 0.33 micromol x L(-1), P < 0.001) compared with the baseline value. The selenium concentration in urine (0.07 +/- 0.02 vs. 18.53 +/- 2.56 micromol x L(-1), P < 0.001), the amount of Se excreted (0.14 +/- 0.07 vs. 21.40 +/- 2.31 nmol x min(-1), P < 0.001) and the renal clearance of Se (0.1 9 +/- 0.03 vs. 3.01 +/- 0.34 mL x min(-1), P < 0.001) were found to be highly significantly elevated during selenite loading. The clearance measurements showed no changes in the urinary flow rate or in the glomerular filtration rate. During and at the end of infusion the highest Se level was attained in plasma, followed by whole blood and RBC. The plasma Se level fell rapidly within 10 min after the end of infusion, but the concentration of Se in RBC was stable up to the fourth hour, when it started to decrease too. On day 5 the Se concentrations in plasma, RBC and whole blood were found to be only slightly but still significantly higher than before the selenite infusion. The large disproportion between the infusion rate of Se (8.76 microg x min(-1)) and its renal excretion rate (1.69 microg x min(-1)) found in clearance measurements suggests low glomerular filtration of infused selenium, which might primarily be caused by the binding of selenite metabolites to blood constituents. The presented results confirm the low bioavailability to ruminants of Se from sodium selenite.     

Volume expansion during NOS substrate donation with L-arginine: regulatory offsetting of renal response?

The responses to infusion of nitric oxide synthase substrate (L-arginine 3 mg.kg(-1).min(-1)) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. L-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 +/- 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 +/- 0.0 to 0.7 +/- 0.1 ml/min). Volume expansion increased arterial blood pressure (102 +/- 3 to 114 +/- 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 +/- 31 micromol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 +/- 1.7 to 1.6 +/- 0.3 pg/ml). Combined volume expansion and L-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 +/- 23 micromol/min at plasma ANG II levels of 3.0 +/- 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, L-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus L-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.     

Effects of mimosine, a potential chemical defleecing agent, on wool growth and the skin of sheep.

Twenty-two Merino sheep were dosed with various amounts of L-mimosine, given either as an intravenous or an intraperitoneal injection, or as a continuous intravenous infusion for periods of 1-4 days. Single injections of mimosine (1-16 g) had no effect on the strength of wool, and wool growth rates were not appreciably altered by injections of small amounts (4 g or less). Injections of larger amounts slightly reduced both length growth rate and diameter of tibres during the 4 days after dosing. The effects of intravenous infusions of mimosine depended on the rate and the duration of administration. Small amounts (0.5 or 1 g/day given for 4 days) has no effects on the strength of wool or on wool growth rates. Infusions of a total of 8 g, either at the rate of 2 or 8 g/day, weakened the wool but not sufficiently to allow the sheep to be defleeced. Both these treatments caused a temporary reduction in length growth rate and in diameter of fibres, and transient degenerative changes were observed in wool follicles. A region of the fibres representing 1-2 days' growth was constricted to about half the pre-infusion diameter when 8 g was given for 1 day. Infusions of at least 8 g mimosine over a period of 1 1/2-2 days were effective for defleecing all sheep dosed. This corresponded to a daily rate of infusion of about 80 mg/kg. No toxic effects were observed with infusions given for periods of 2 days. Defleecing was judged to be possible by 6-7 days after the start of infusion, and was readily carried out by about 14 days. Defleecing was associated with follicle retrogression and an abrupt cessation of wool growth within 2 days of the start of the infusions. It was estimated that fibre growth stopped for about 10 dyas; regrowth was first observed 17-18 days from the beginning of dosing. Low rates of infusion of mimosine (up to 2 g/day) resulted in plasma levels below 0.1 mmol/l. Infusion at the rate of 4 g/day or above, which produced defleecing, quickly resulted in levels of mimosine in plasma above 0.1 mmol/l; after 2 days the concentration was steady at aboug 0.2 mmol/l. Injections of 8 or 16 g mimosine resulted in very large, but transient, rises of the level in plasma.     

Plasma and urinary clearance rates of atrial natriuretic factor during ontogeny in sheep

The present study was designed to determine the plasma clearance rate of atrial natriuretic factor (ANF) during development in chronically-instrumented fetal, newborn and adult non-pregnant sheep. To determine the contribution of the kidney in the metabolism of ANF, urinary clearance of ANF was also measured. Intravenous infusion of ANF (0.025 and 0.1 microgram.min-1.kg-1) produced a significant decrease in mean arterial blood pressure in newborn lambs and in adult non-pregnant sheep. Estimated plasma ANF clearance rate for the 0.025 and 0.1 microgram.min-1.kg-1 ANF infusion rate were respectively 177 +/- 55 and 155 +/- 34 ml.min-1.kg-1 in fetuses, 138 +/- 26 and 97 +/- 13 ml.min-1.kg-1 in newborn lambs and, 148 +/- 33 and 103 +/- 25 ml.min-1.kg-1 in adult nonpregnant ewes. Fetal, newborn and adult ANF plasma clearance rates during high ANF infusion rate (0.1 microgram.min-1.kg-1) were not significantly different. Low or high ANF infusion rate was not associated with significant changes in urinary ANF concentration or urinary ANF excretion rate. Taken together, the present study demonstrates that ANF plasma clearance rate is similar in fetal, newborn and adult non-pregnant sheep and that the excretory function of the kidney contributes only minimally to ANF plasma clearance rate.     

Changes in the relationship between cerebrospinal fluid and blood composition produced by ACTH treatment in conscious sheep

It has been proposed that an increase in CSF osmolality could be involved in the genesis of hypertension by activation of central nervous system receptors involved in cardiovascular regulation. ACTH induced hypertension in the sheep is an adrenally dependent model of steroid induced hypertension. This study reports the effect of ACTH administration (20 g/kg/day) for 5 days on the composition of cerebrospinal fluid (CSF) and blood (plasma) in conscious sheep. ACTH increased CSF and plasma osmolality within 24 h associated with parallel increases in both blood and CSF glucose concentrations and plasma and CSF sodium concentration. Plasma potassium fell within 24 h, but CSF potassium did not change over the 5 days of ACTH treatment. Neither calcium nor magnesium changed in either plasma or CSF. CSF phosphate increased and plasma phosphate decreased. CSF and plasma bicarbonate were elevated with ACTH. Plasma chloride decreased after 5 days of ACTH treatment but was not associated with a change in CSF. The relevance of the measured changes in CSF osmolality and composition to the mechanisms involved in the production of ACTH-induced hypertension will be subject of further experimentation.     

Effects of truncated angiotensins in humans after double blockade of the renin system

Angiotensins different from ANG II exhibit biological activities, possibly mediated via receptors other than ANG II receptors. We studied the effects of 3-h infusions of ANG III, ANG-(1-7), and ANG IV in doses equimolar to physiological amounts of ANG II (3 pmol. kg-1. min-1), in six men on low-sodium diet (30 mmol/day). The subjects were acutely pretreated with canrenoate and captopril to inhibit aldosterone actions and ANG II synthesis, respectively. ANG II infusion increased plasma angiotensin immunoreactivity to 53 +/- 6 pg/ml (+490%), plasma aldosterone to 342 +/- 38 pg/ml (+109%), and blood pressure by 27%. Glomerular filtration rate decreased by 16%. Concomitantly, clearance of endogenous lithium fell by 66%, and fractional proximal reabsorption of sodium increased from 77 to 92%; absolute proximal reabsorption rate of sodium remained constant. ANG II decreased sodium excretion by 70%, potassium excretion by 50%, and urine flow by 80%, whereas urine osmolality increased. ANG III also increased plasma aldosterone markedly (+45%), however, without measurable changes in angiotensin immunoreactivity, glomerular filtration rate, or renal excretion rates. During vehicle infusion, plasma renin activity decreased markedly ( approximately 700 to approximately 200 mIU/l); only ANG II enhanced this decrease. ANG-(1-7) and ANG IV did not change any of the measured variables persistently. It is concluded that 1) ANG III and ANG IV are cleared much faster from plasma than ANG II, 2) ANG II causes hypofiltration, urinary concentration, and sodium and potassium retention at constant plasma concentrations of vasopressin and atrial natriuretic peptide, and 3) a very small increase in the concentration of ANG III, undetectable by usual techniques, may increase aldosterone secretion substantially.     

Central effects of atrial natriuretic peptide on plasma catecholamines, vasopressin, renin and beta-endorphin and on renal excretory functions in the dog

Atrial natriuretic peptide (ANP) has been identified in the central nervous system and its participation in regulation of various regulatory brain functions has been postulated. To elucidate whether central ANP influences endocrine systems related to blood pressure regulation and renal excretory functions, effects of infusion of ANP at a rate of 120 ng.min-1 into the third cerebral ventricle on plasma level of epinephrine (E), norepinephrine (NE), renin, vasopressin and beta-endorphin as well as on excretion of urine, sodium, potassium (UKV) solutes and free water (CH2O) were investigated in conscious dogs. Significant decrease of plasma E from 77.6 +/- 7.0 to 62.1 +/- 4.8 pg.ml-1 and of NE from 345.5 +/- 20.7 to 286.4 +/- 15.0 pg.ml-1 was found at the end of 30 min lasting ANP infusion. Significant elevation of PRA and UKV and a decrease in CH2O were found 60 min after ANP infusion. No significant changes in other variables were found. In time control experiments plasma hormones concentration and renal excretory functions were not significantly influenced. The results suggest that central ANP may affect the sympatho-adrenal outflow.     

Effect of prostaglandin A1 infusion in hypertensive patients with renal artery stenosis

Clinical data, arteriographic findings, peripheral and renal vein plasma renin activity (PRA) studies and responses to prostaglandin A1 infusion are presented from observations in seven hypertensive patients with renal artery stenosis. PGA1 infusion caused an increase in PRA and urine sodium excretion but no significant change in blood pressure. Exaggerated increases in PRA were observed in five patients. With cessation of PGA1 infusion PRA returned toward pre-infusion levels. In two patients bilateral renal and peripheral vein PRA's were determined before and during PGA1 infusion. PGA1 caused a greater increase in renal vein PRA than in peripheral vein PRA indicating a direct enhancement of renin secretion. These studies indicate possible relationships between the vasoactive prostaglandins and the renin-angiotensin system in the pathogenesis of hypertension due to renal artery stenosis.