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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A denervated 'auto-transplanted' dog's kidney preparation was developed to study renin release into renal plasma and lymph. The function of the 'transplant' was compared with that of its partner. In the 'basal' state it had a similar rate of plasma and urine flow, Na, Ca, Mg and Cl excretion but a lower rate of glomerular filtration and K excretion and a lower urinary osmolality. In the 'basal' state the 'transplant' did not release renin into plasma, but invariably released it into lymph. 2. Infusions of MgCl2 solutions into the renal artery which raised the renal plasma Mg concentration (PMg) by 0.1-2 m-mole.1.-1 provoked a concentration-related increase in renin release into plasma. This was due to a rise in the veno-arterial renin difference and in the renal plasma flow rate. Blood pressure and Na excretion were unaltered. 3. In other experiments, an increase in PMg of 1.5-2.5 m-mole.1.-1 was also found to increase renin release into lymph. 4. When the plasma Ca concentration was doubled by infusion of CaCl2 into one renal artery, an increase in PMg of 1.5-2.5 m-mole.1.-1 no longer increased renin release into plasma or lymph. 5. When the plasma NaCl concentration was raised by 8-15 m-mole.1.-1 by infusion of hypertonic saline into the renal artery, MgCl2 infusion failed to increase renin release until PMg was raised by more than 3 m-mole.1-1. 6. The results demonstrate that hypermagnesaemia stimulates renal renin release by a mechanism that is independent of the renal nerves, or of any changes in blood pressure or sodium excretion, but which is antagonized by concurrent hypercalcaemia or hypersalaemia. The possibility is discussed that Mg is reabsorbed from the tubular into the interstitial fluid where it antagonizes the action(s) of Ca on renin release from the juxtaglomerular cells.
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PMID:The effect of increasing the plasma magnesium concentration on renin release from the dog's kidney: interactions with calcium and sodium. 36 8

1. Intracranial injections of the individual components of the renin-angiotensin system caused drinking in water-replete dogs. 2. Angiotensin II was the most reliable, potent and rapidly acting intracranial dipsogen and elicited drinking in the absence of peripheral circulatory changes. After the highest dose of angiotensin II (10(-9) mole) five dogs drank a mean amount of 380.0 +/- 88.6 ml. For the other components, the order of dipsogenic effectiveness was angiotensin I, synthetic renin substrate, and angiotensin III. 3. Isotonic saline, bradykinin (10(-10) mole), eledosin-hexapeptide (10(-10) mole), oxytocin (10(-10) mole) and prostaglandin F2alpha (1-200 X 10(-12) mole) were ineffective. 4. Intracranial renin (10 m-u.) produced a mean intake of 445 +/- 152 ml. of water in eight dogs. 5. Dog renin substrate and synthetic renin substrate, injected intracranially in a dose of 10(-10) mole, produced similar intakes of water but these amounts were very much less than the volume drunk in response to the same dose of angiotensin II. 6. None of the components injected into dipsogenically responsive sites in the brain caused changes in blood pressure, although the act of drinking itself produced a small rise. 7. Angiotensin II at the highest dose produced drinking when injected into the subfornical organ, preoptic region, anterior hypothalamus, lateral ventricle, third ventricle, ventral hippocampus and mid-line thalamus. Negative sites were found in the caudate nucleus, fourth ventricle, mid-brain, posterior thalamus, dorsal hippocampus, lateral hypothalamus and posterior hypothalamus. 8. After the lowest dose of intracranial angiotensin II (10(-12) mole) only the preoptic region and subfornical orgal were responsive. These two sites were equally sensitive in terms of latency and amounts drunk at all doses injected. 9. Angiotensin did not necessarily have to reach a cerebral ventricle in order to cause drinking. 10. The dog resembles the rat in its responsiveness to the dipsogenic action of intracranial angiotensin II. The regions of the brain from which drinking can be elicited are more widespread than has been claimed by some in the rat.
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PMID:Drinking and haemodynamic changes induced in the dog by intracranial injection of components of the renin-angiotensin system. 65 Apr 66

1. Intravenous infusion of the individual components of the renin-angiotensin system caused drinking in dogs in water balance. 2. Angiotensin II was the most potent and rapidly acting peptide inducing drinking. The minimum effective rate of infusion was between 8.3 and 16.6 X 10(-12) mole kg-1 min-1 which yield blood levels of angiotensin II that fell well within physiological limits for the dog and were mildly pressor. Angiotensin I and synthetic renin substrate caused less drinking than angiotensin II, and angiotensin III was the least effective dipsogen. 3. Renin caused significant drinking when infused I.V. at a rate of 0.5 u. min-1 for 15 min. Drinking was slower in onset and continued for longer than after other components of the renin-angiotensin system. 4. Within the dose range 1875-15,000 X 10(-12) mole of angiotensin II the amount of water drunk depended more on the rate of infusion than on the duration of the infusion. 5. During an I.V. infusion of angiotensin II lasting 2 hr, the rate of drinking was greatest during the first 15 min. After this declined progressively. 6. A delay of 1 hr after the start of an intravenous infusion of angiotensin II before access to water was allowed, did not significantly reduce the amount of water drunk. Nor did infusion of isotonic saline for 105 min reduce drinking in response to a subsequent infusion of angiotensin II. However, a preload of dilute milk approximately equal in volume to the amount of water normally drunk in response to I.V. angiotensin II significantly reduced drinking. Therefore the dog stopped drinking during long-term infusions of angiotensin II owing to the action of satiety mechanisms and not to tachyphylaxis or fatigue. 7. Intracarotid infusion of angiotensin II, angiotensin I, synthetic renin substrate and angiotensin III, at 40 X 10(-12) mole min-1 also caused drinking. Intakes of water were similar to the intakes after I.V. infusion at six times the arterial rate, except that angiotensin I was relatively less effective by intracarotid infusion than by I.V. infusion. 8. Renin, infused at 0.5 u. min-1 for 15 min, was much less effective by intracarotid infusion than by intravenous. 9. These results are compatible with a role for circulating angiotensin II in the thirst of hypovolaemia or moderate extracellular dehydration.
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PMID:Systemic angiotensin-induced drinking in the dog: a physiological phenomenon. 65 Apr 70

1. An experimental technique utilizing 'denervation diuresis' from one kidney with measurement of renin release from the contralateral innervated kidney was developed to study the sensitivity of renin secretion to volume depletion. 2. With urine excretion, release of renin increased progressively from the innervated kidney. The increase was significant at a sodium deficit of 0-23 mole.kg-1. At a sodium deficit of 0-6 m-mole.kg-1 renin release had doubled. 3. Bilateral vagotomy did not alter this response. 4. Precise replacement of sodium loss with isotonic saline but without replacement of other urinary components returned renin release to control levels. 5. Slow haemorrhage causing a rate of volume and sodium loss equivalent to urinary drainage did not alter the rate of renin release. 6. With a single denervated kidney and contralateral nephrectomy, renin release fell progressively to minimal levels despite sodium deficits up to 2-6 m-mole.kg-1. 7. It is concluded that renin secretion is sensitive to at most a 0-5% change in body fluid volume and should be considered a primary response to volume depletion. The sensitivity of the response depends upon normal renal innervation but is not mediated via vascular volume receptors nor via receptors innervated by the vagus. 8. It is proposed that the extreme sensitivity of the renin-secreting system in these experiments results from the combination of volume depletion and slight hypotonicity of extracellular fluid acting on the renal afferent arteriole without the mediation of the macula densa,
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PMID:Sensitivity of renin secretion to volume depletion in the anaesthetized dog: comparison between urinary drainage and slow haemorrhage. 95 49

The interaction between mouse submaxillary gland renin and a statine-containing, iodinated substrate analog inhibitor was studied. The compound, 1 (Boc-His-Pro-Phe-(4-iodo)-Phe-Sta-Leu-Phe-NH2, Sta = (3S,4S)-4-amino-3-hydroxy-6-methyl-heptanoic acid), a statine-containing analog of the renin substrate octapeptide, was a competitive inhibitor of cleavage of synthetic tetradecapeptide renin substrate by mouse submaxillary gland renin, with a Ki of 6.2 x 10(-10) M (pH 7.2, 37 degrees C). Titration of the partial quenching of the tryptophan fluorescence of the enzyme by 1 revealed tight binding with a dissociation constant less than 3 nM and a binding stoichiometry of one mole 1 per mole enzyme. The time course of tight binding of 1 to mouse renin appeared to be fast, with kON greater than or equal to 1.3 x 10(6) s-1 M-1. The UV difference spectrum generated upon binding of 1 to mouse renin had two prominent features: a strong, broad band that had a minimum at 242 nm with delta epsilon (242) = -19,500 cm-1 M-1, and a triplet of enhanced bands centered at 286 nm with delta epsilon (286) about +1100 cm-1 M-1. The strong, broad, negative band was similar to the difference between the UV absorbance of 1 in methanol and in 0.1 M citrate phosphate pH 7.2. A structure-activity correlation for analogs of 1 showed some moieties of 1 that are important for potent inhibition of mouse renin. The inhibition data for these compounds versus human kidney renin suggested that the solution of the crystal structure of 1 bound to mouse renin will provide useful information for the design of inhibitors of human kidney renin.
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PMID:Interaction of mouse submaxillary gland renin with a statine-containing, subnanomolar, competitive inhibitor. 391 10

1. When applied directly to the brain, angiotensin II amide, as either the valine(5) octapeptide, causes rats in normal fluid balance to drink water.2. The drinking response to angiotensin injections is copious, rapid, repeatable within the same test session, and stable over months of testing in the same animal.3. The response is motivationally potent and specific. After injection the animals move directly to the source of water and drink. There is typically no preliminary hyperactivity or subsequent depression. The animals do not eat, gnaw or exhibit other behaviours that are not normally seen during spontaneous drinking. The injections rouse sleeping animals to drink and interrupt eating in animals deprived of food for two days.4. The region of the brain that is most sensitive to angiotensin includes the anterior hypothalamus, the preoptic region, and the septum including the nucleus accumbens.5. Intracranial renin elicited drinking. Bradykinin and vasopressin did not, nor did adrenaline, noradrenaline or aldosterone. In the most sensitive region, sites positive for angiotensin also yielded drinking to carbachol.6. Responses were obtained with 5 ng (ca. 5 p-mole) and occurred reliably with 50 ng angiotensin or more. The dose-response curve for amount drunk rose from 5 to 100 ng and levelled off thereafter. Angiotensin is therefore the most potent dipsogen known and is effective at doses that are reasonably within the concentration range for circulating endogenous angiotensin.7. Injections into the sensitive region of doses of angiotensin that were effective for drinking did not produce peripheral haemodynamic changes in lightly anaesthetized rats.8. This work strengthens the suggestion that angiotensin is a natural hormone of drinking behaviour that participates in extracellular thirst by its release from the kidney and subsequent direct action on a specific chemoreceptive region in the anterior diencephalon and limbic lobe.
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PMID:Drinking induced by injection of angiotensin into the rain of the rat. 432 23

1. The pigeon drank as vigorously in response to intracranial injection of synthetic renin substrate and angiotensin I as to angiotensin II. 2. Mammalian renin injected into the brain caused the water-replete pigeon to drink but it was a less effective dipsogen than in the mammal. As in the mammal, renin-induced drinking was slower in onset and continued for longer than angiotensin-induced drinking. 3. The converting enzyme inhibitor SQ 20881 attenuated drinking in response to intracranial renin, synthetic renin substrate and angiotensin I but enhanced intracranial angiotensin II-induced drinking. Therefore drinking induced by the intracranial injection of precursors of angiotensin II is mediated through local generation of angiotensin II. 4. I.V. injection of angiotensin I was as effective as angiotensin II in causing the pigeon to drink, but synthetic renin substrate was less effective. I.V. doses of angiotensin I and II had to be about 100 times greater than the intracranial doses in order to produce similar intakes. 5. Angiotensin I and II were equally effective pressor agents by I.V. injection in the pigeon but synthetic renin substrate was much less effective. I.V. SQ 20881 inhibited the pressor response to I.V. synthetic renin substrate or angiotensin I but enhanced the angiotensin II-induced response. 6. Aliphatic position 8-substituted analogues of angiotensin II which are competitive antagonists of angiotensin II-induced drinking and pressor responses in the mammal in antagonist:agonist mole ratios as low as 10:1, failed to reduce drinking in response to intracranial synthetic renin substrate or angiotensin II, although not themselves agonists, nor did they prevent the pressor to infusion of angiotensin II even with antagonist:agonist mole ratios as high as 10,000:1. 7. Shortening the angiotensin octapeptide from the N-terminus caused a progressive reduction in intracranial dipsogenic activity. Activity was completely abolished by removing the C-terminal phenylalanine. 8. These results demonstrate that in pigeons, as in mammals, it is angiotensin II which is the biologically active peptide in the control of drinking behaviour and blood pressure by the renin-angiotensin system. Precursors of angiotensin II can be converted to the octapeptide in the avian brain as well as in the circulation. The angiotensin receptors for drinking and blood pressure responses are similar to each other in the pigeon and they are very similar but not identical with the angiotensin receptors for the dipsogenic, pressor and myotropic actions of angiotensin II in mammals.
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PMID:Drinking and changes in blood pressure in response to precursors, fragments and analogues of angiotensin II in the pigeon Columba livia. 616 84

The effects of vanadate on cardiovascular function and on the secretion of renin and vasopressin were investigated by infusing sodium orthovanadate (0.32 mu mole/kg X min) intravenously into five conscious dogs. Vanadate caused significant increases in mean arterial pressure, total peripheral resistance, pulmonary arterial pressure, and cardiac output. These data illustrate that the hemodynamic effects of vanadate in the conscious dog are similar to those of the anesthetized dog but that minor differences do exist. Vanadate significantly suppressed plasma renin activity, but plasma vasopressin was unchanged. The effects of vanadate also were investigated in the same dogs on another day after administration of the calcium channel blocker, verapamil (0.3 mg/kg bolus + 0.01 mg/kg X min). After calcium channel blockade, the increases in arterial pressure and pulmonary arterial pressure induced by vanadate were attenuated, and cardiac output did not increase. Calcium channel blockade also prevented the vanadate-induced decrease in plasma renin activity. These data suggest that the cardiovascular and humoral alterations produced by vanadate in the conscious dog are at least partially mediated by changes in intracellular calcium.
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PMID:Cardiovascular and renin responses to vanadate in the conscious dog: attenuation after calcium channel blockade. 636 50

A total of 16 normal subjects and 30 patients with IB (labile hypertension) and IIB (stable hypertension) stages of essential hypertension during excessive salt intake as well as 13 normal persons and 43 patients at the labile and stable stages of essential hypertension on usual salt diet were examined. Renin activity, plasma aldosterone and cortisol levels were studied using radioimmunoassay in the basal conditions and 1 and 5 hours later after intravenous administration of 5% saline solution (3,6-3,8 mu mole of sodium (1 kg body mass). It was demonstrated that the prolonged excessive intake of sodium hydrochloride resulted in the alteration of the functional state of the renin-angiotensin-aldosterone system even in the normal persons. The above alterations are characterized by the loss of the adequate response of the renin-angiotensin system and the adrenal cortex to the increased sodium concentration, and extracellular fluid volume in the body, as well as by the separation of the functions of these two humoral systems.
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PMID:[Effect of salt on the functional state of the renin-angiotensin-aldosterone system in healthy persons and hypertensives]. 702 16

The effects of feeding 9% beef tallow (BT) or menhaden oil (MO) in a 10% fat-60% sucrose-20% protein diet on renal cortex fatty acid profile, renal lipid peroxide formation potential, and the blood pressure response to a norepinephrine challenge was studied. Male weanling BHE/cdb prediabetic rats were studied after 8 weeks of diet treatment. Half the rats were subjected to a norepinephrine challenge, and their mean arterial blood pressure was determined. Plasma renin and angiotensin II levels were determined in the presence or absence of the challenge. The source of dietary fat had no effect on these measurements. MO fed rats had a greater potential to form lipid free radicals in the kidney than BT fed rats despite the fact that the renal tissue from both groups had an equivalent number of unsaturations on a mole % basis. From these results we conclude that the accelerated renal disease in menhaden oil fed rats is not due to a diet fat effect on blood pressure regulation but might be due to a diet fat effect on free radical production. These free radicals can be cytotoxic and if produced in large amounts could result in a loss of glomerular cells. Whether this occurs and can be reversed by a change in diet was not determined.
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PMID:Menhaden oil feeding increases potential for renal free radical production in BHE/cdb rats. 763 49


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