Acute Saline Research Articles

271 THE EFFECT OF ACUTE EXTRACELLULAR VOLUME EXPANSION ON MTOCARDIAL GLYCOGEN IN THE NEWBORN RAT

Glucose and its metabolites are the principal cardiac energy substrates in the fetus and neonate. Anoxia and adrenergic stimulation have been shown to deplete myocardial glycogen stores, but the effect of extracellular volume expansion on carbohydrate metabolism has not been previously studied. The effect of acute saline loading on myocardial glycogen concentration was studied in 8 littermate pairs of newborn rats, matched for age. One member of each pair, assigned to the experimental group, received an intraperitoneal bolus injection of isotonic saline, 80 ml/kg body weight. The remaining member (control) received a multielectrolyte maintenance solution, 8.4 ml/kg, in the same manner. At 2 hours, the animals were sacrificed and the hearts excised and weighed. Myocardial glycogen was assayed using a modification of the glucose oxidase method. No significant difference in cardiac weight was noted between groups (exp=.064±.003 SEM gm, cont=.057±.011gm). The glucose concentration in mg/dl/gm wet weight tissue was 176.4±17.9 in exp group and 257.7±94.4 in the cont group (p<.05). The finding of lower myocardial glucose content in the saline loaded rats in the absence of a significant increase in water content, suggests that acute extracellular volume expansion exerts a significant effect on cardiac carbohydrate metabolism in newborns.

The effect of acute saline volume expansion on renal Na-K-ATPase.

To examine the role of Na-K-ATPase in the natriuresis that occurs after acute extracellular volume expansion, we performed acute clearance experiments and in vitro analysis of renal microsomal ATPase activity in rats receiving intravenous 0.9% sodium chloride (0.1 ml/100 g bw/min). Despite increased absolute reabsorption of filtered sodium (196 +/- 8.1 vs. 165 +/- 11.4 uEq/min, p less than 0.05), renal medullary microsomal Na-K-ATPase activity was decreased from 134 +/- 5.9 to 110 +/- 6.3 pmol Pi/mg protein/hour (p less than 0.02). No changes occurred in cortical or papillary regions and Mg-ATPase was unaffected. Similar results were obtained after adding 4 mEq/l potassium chloride to the infusion to prevent any fall in serum K+. These data suggest that a considerable percentage of sodium reabsorption is suppressed in acutely volume expanded animals and it is proposed that this is mediated by inhibition of medullary Na-K-ATPase.

Inhibitory effects of harvested proximal tubular fluid on Jv and delta cNa during acute saline volume expansion in the rat.

The present micropuncture experiments were carried out in male Wistar rats during isotonic saline volume expansion (VE) to explore the relative importance of peritubular physical forces and tubular factors on proximal tubular Na transport. Isotonic volume flux, measured by the shrinking drop technique was reduced from 3.53 +/- 0.09 X 10(-4) . mm3 . mm-2 . s-1 with the artificial fluid to 1.79 +/- 0.1 with harvested autologous proximal tubular fluid (HTF) (49%), but only to 2.77 +/- 0.1 (78% of control) with artificial tubular solution (AS), both during volume expansion. delta cNa was reduced from a control of 18.0 +/- 2.2 mmol . kg-1 -14.5 +/- 2.0 with AS (81%) and 10.0 +/- 2.4 with HTF (56%) during VE. Thus both isotonic volume flux as well as delta cNa were reduced to the same degree by saline VE. These results and those obtained previously with mannitol-saline VE, indicate the presence of a factor in harvested proximal tubular fluid of volume expanded rats which inhibits sodium and water transport independent of peritubular osmolarity.

The influence of isotonic saline administration on the urinary excretion of kallikrein in rats

Acute saline loading is known to increase kallikrein excretion. To clarify whether this is a specific stimulatory effect or rather a non-specific wash-out, pentobarbital anesthetized rats were loaded thrice (5 min infusions) at 40 min intervals with a volume of 150 mM NaCl equal to 5% of their body wt. The effect of such a load on the central venous pressure was studied in a separate group of rats. Control animals did not receive the infusions. Kallikrein excretion (amidolytic assay) increased with the first, but decreased with the subsequent saline administrations. The rise observed after the first load lost significance when kallikrein excretion was related to that of creatinine. The reduction observed after the second and third infusions remained significant even when expressed per mg of creatinine. Thus, saline load induced kallikrein “stimulation” is due to a non-specific wash-out. Similar transient enhancements of central venous pressure were observed after each of the three loads. This, together with the unchanged creatinine excretion (except for the rise seen after the first load) indicate that the lack of kallikrein stimulation after the second and third loads was not due to the appearance of heart failure. Saline loaded rats had a renal kallikrein activity at the end of the experiment which did not differ from that of controls. Plasma aldosterone concentration was reduced in saline infused rats, and it correlated with the kallikrein excretion when both, NaCl loaded and control rats, were taken into account.

Urinary kallikrein response to acute saline or water loads in hypertensive and normal humans.

Urinary kallikrein response to acute saline or water loads in hypertensive and normal humans.

Urinary kallikrein response to acute saline or water loads in hypertensive and normal humans.

Urinary kallikrein excretion during acute water or saline loading was studied in normal and hypertensive humans after chronic Na+ depletion and Na+ loading to answer the following questions. 1. Is urinary kallikrein a natriuretic or diuretic substance? 2. During acute water or saline loading, does the underlying Na+ balance influence (a) the urinary kallikrein response? or (b) the relationship between urinary kallikrein and renal Na+ or water handling? 1) Urinary kallikrein did not change during a 1.2 liter water load given to nine white hypertensive and five white normal men. Urinary kallikrein was significantly decreased, however, in five white hypertensive and five white normal subjects during and after 1 hour of isotonic saline infusion (30 ml/kg). In sodium-depleted hypertensive patients kallikrein excretion was decreased from 19.8 to 9.5 mEU /min, and in Na+-depleted normal subjects it was decreased from 15.7 to 12.6 mEU /min (p = 0.003). The response in hypertensive patients was not different from normal subjects. In all Na+-loaded subjects, kallikrein excretion was also significantly decreased during isotonic saline infusion (p = 0.01). Urinary kallikrein did not change in three other subjects given hypertonic saline. 2(a) The underlying state of Na+ balance influenced the baseline level of kallikrein excretion, but not the directional decline in kallikrein during isotonic saline. (b) In Na+-restricted hypertensives given isotonic saline, urinary kallikrein was inversely related to the fractional excretion of Na+ (r = -0.54, p less than 0.01) and the tubular reabsorption of H2O (TcH2O/GFR; r = -0.50, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Acute Saline Expansion on the Fractional Sodium Excretion (FE&lt;sub&gt;Na&lt;/sub&gt;) and the Renal Efferent Sympathetic Nerve Activity (RSNA) in Spontaneously Hypertensive Rat (SHR)

1. SHR demonstrated exaggerated natriuresis with acute saline expansion. 2. RSNA in SHR was more inhibited than in WKY after acute saline expansion. 3. Therefore, RSNA in SHR may also be involved in the expression of exaggerated natriuresis with acute saline expansion.

Enhancement of sodium excretion by substance P during saline loading in the canine puppy.

Summary: Saline loading in puppies results in an attenuated natriuresis when compared to the normal response by adult animals to the same degree of volume expansion. To characterize an eventual role for kinins in the diuretic response by puppies to saline loading, two experimental protocols were constructed to evaluate the effect of substance P infusion during baseline hydration and acute saline loading. Low dose (10 ng·kg−1·min−1) infusion of substance P during basal conditions did not affect urine flow, sodium excretion or glomerular filtration rate (GFR). The addition of saline loading to the ongoing low dose infusion of substance P produced an increase in urine flow from 3.73 to 12 μ l·min−1·g−1 kidney weight and resulted in a marked increase in urinary sodium excretion from 110 to 851 μ Eq·min−1·g−1 kidney weight. These increases in urine flow and urinary sodium excretion during low dose substance P infusion were significantly greater than those observed during saline loading alone. No significant effect on GFR was observed during either saline loading alone or low dose substance P during saline loading. In Protocol II, the infusion of low dose substance P during an ongoing saline load enhanced diuresis and natriuresis to a greater extent than those receiving only a saline load without affecting GFR. The high dose infusion of substance P (100 ng·kg−1·min−1) during baseline hydration resulted in a natriuresis and diuresis that persisted during the addition of saline despite a significant fall in GFR. Saline loading alone resulted in increased urinary kallikrein activity and the infusion of substance P (10 ng·kg−1·min−1) increased urinary kallikrein activity even further. A significant positive correlation between urinary sodium excretion and urine kallikrein activity was found (r = 0.91, P < 0.01).

Renal Functional and Metabolic Studies on the Role of Preventive Measures in Experimental Acute Ischemic Renal Failure

In the present study 1 h of total occlusion of the left renal artery in conscious rats was chosen as experimental model of ischemic acute renal failure (ARF), while the contralateral kidney was left intact. Chronic high dietary sodium intake, acute isotonic saline infusion, or administration of saralasin did not protect from ARF. Furosemide, mannitol, and verapamil converted oliguric into non-oliguric ARF in 100%, 75%, and 60% of the animals, resp. Protection from oliguria and preservation of GFR inversely correlated with the depression of cortical ATP-concentration (control: 1.32 +/- 0.07 mumoles/g wet weight) 6 h after ischemia by 16%, 41%, and 58% in mannitol- and verapamil- treated rats and in untreated rats, resp. At this time, Na-K-ATPase enzyme activities in renal cortex and papilla were unaffected, while enzyme activity in outer medulla was suppressed from 15.4 +/- 1.4 to 9.4 +/- 1.0 mumoles Pi/mg protein h in all groups of animals. The results suggest that in this model of ARF renal ischemia not only affects cellular energy supply in renal cortex but also causes severe structural and functional impairment in the outer medulla, probably leading to tubular obstruction and depression of glomerular function. Pharmacological protection from ischemic oliguric ARF cannot be achieved by prior induction of high urine flow rates alone but depends on the degree of metabolic and functional reserve of the injured tubular epithelium.

Effect of Captopril on the Blood Pressure and Renal Responses to Acute Saline Loading in Normal and Essential Hypertensive Subjects

1. Systemic, humoral and renal responses to isotonic volume expansion (1800 ml in 3 h) were assessed in normal subjects and patients with normal renin essential hypertension before and during captopril administration. 2. Essential hypertensive subjects had a greater natriuretic and diuretic response to volume expansion than had normotensive subjects. 3. Captopril induced a fall in pre-saline mean arterial pressure more marked in hypertensive (20 ± 3 mmHg) than in normotensive subjects (9 ± 2 mmHg) and did not produce any change in sodium balance. 4. Captopril exaggerated the response of arterial pressure to volume expansion since mean arterial pressure increased more markedly after than before captopril in both normotensive (18.7 ± 3.8%) and hypertensive subjects (16.9 ± 3.7%). 5. Captopril blunted the exaggerated natriuretic response to volume expansion observed in patients with essential hypertension, whereas the renal response was unchanged in normotensive subjects.

The Effects of Acute Intravenous Saline Infusion in Hypertensive and Normotensive Renal Transplant Recipients

The Effects of Acute Intravenous Saline Infusion in Hypertensive and Normotensive Renal Transplant Recipients

Absence of production of natriuretic factor following acute saline expansion in nephrotic rats.

1. The natriuretic activity of an extract from the kidneys was studied in control and nephrotic rats following acute saline expansion. 2. The natriuretic effect of a known natriuretic material prepared from human urine was evaluated in control and nephrotic rats. 3. After actute saline expansion, natriuretic activity was obtained only from the fractions extracted from the kidneys of the control rats. 4. Injection of natriuretic material produced a equal natriuretic response in both control and nephrotic rats.

Postural hypotension during tilt with chronic captopril and diuretic therapy of severe congestive heart failure

The hemodynamic mechanism by which patients with chronic congestive heart failure (CHF) maintain their blood pressure (BP) in the upright posture is distinct from that of normal and hypertensive individuals. There are little data regarding the effects of chronic vasodilator therapy on the mechanisms controlling this response, especially in the presence of diuretic therapy. Therefore, 10 consecutive patients with severe chronic CHF underwent hemodynamic tilt study following acute and chronic captopril therapy. One patient developed orthostatic hypotension following first-dose captopril, but 6 of 10 had a mean BP decrease of 70 ± 6 to 56 ± 3 mm Hg on tilt following chronic captopril. This was associated with significant reduction of plasma aldosterone, and was abolished on re-tilt following acute saline infusion. Therefore, during chronic captopril therapy of CHF, a reduction of diuretic dosage may be necessary to prevent orthostatic hypotension.

Reversal by a dopamine antagonist of saline-induced attenuation of aldosterone response to angiotensin II infusion in man.

In an attempt to elucidate the dopaminergic involvement in the regulation of the effect of angiotensin II on the adrenals, plasma aldosterone response to angiotensin II infusion (5 ng/kg/min, for 60 minutes) was studied in five normal volunteers in various experimental conditions. Prior infusion of dopamine (3 micrograms/kg/min) or saline (1000 ml/hour) caused an attenuation of the aldosterone response to angiotensin II. Concurrent infusion of a dopaminergic antagonist, metoclopramide (10 micrograms/kg/min), abolished the inhibitory effect of dopamine and saline. These results suggest that the dopaminergic mechanism is involved in the adaptive aldosterone response of the adrenal to acute saline loading in man.

Reduced sodium excretory ability in young spontaneously hypertensive rats.

The excretory response of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) to acute saline load was compared to that of control Wistar Kyoto rats (WKY) in pre- and early-hypertensive phases. In each of the 3 groups, half of the animals was fed a low salt diet, and the other half a normal diet. At the prehypertensive phase, sodium and water excretion and sodium-potassium ratio in the urine in SHR and SHRSP fed a normal diet were significantly less than those in WKY. The ability of SHR to excrete sodium and water, however, was improved by the elevation of blood pressure that developed between 7 and 10 weeks after their birth. While young SHR fed a normal diet had a reduced ability to excrete sodium, the young SHR fed a sodium-restricted diet did not. Salt restriction significantly delayed the appearance of high blood pressure in both SHR and SHRSP. These results suggest that in both SHR and SHRSP, and elevation of blood pressure is important to compensate for the reduced ability to excrete sodium and water.

REDUCED SODIUM EXCRETORY ABILITY IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

The excretory response of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) to acute saline load was compared to that of control Wistar Kyoto rats (WKY) in pre- and early-hypertensive phases. In each of the 3 groups, half of the animals was fed a low salt diet, and the other half a normal diet. At the prehypertensive phase, sodium and water excretion and sodium-potassium ratio in the urine in SHR and SHRSP fed a normal diet were significantly less than those in WKY. The ability of SH R to excrete sodium and water, however, was improved by the elevation of blood pressure that developed between 7 and 10 weeks after their birth. While young SHR fed a normal diet had a reduced ability to excrete sodium, the young SHR fed a sodium-restricted diet did not. Salt restriction significantly delayed the appearance of high blood pressure in both SHR and SHRSP. These results suggest that in both SHR and SHRSP, an elevation of blood pressure is important to compensate for the reduced ability to excrete sodium and water.

Kallikrein inhibitors decrease short-circuit current by inhibiting sodium uptake.

HomeHypertensionVol. 3, No. 6_pt_2Kallikrein inhibitors decrease short-circuit current by inhibiting sodium uptake. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBKallikrein inhibitors decrease short-circuit current by inhibiting sodium uptake. G G Orce, G A Castillo and H S Margolius G G OrceG G Orce Search for more papers by this author , G A CastilloG A Castillo Search for more papers by this author and H S MargoliusH S Margolius Search for more papers by this author Originally published1 Nov 1981https://doi.org/10.1161/01.HYP.3.6_Pt_2.II-92Hypertension. 1981;3 Previous Back to top Next FiguresReferencesRelatedDetailsCited By Patel A, Chao J and Palmer L (2012) Tissue kallikrein activation of the epithelial Na channel, American Journal of Physiology-Renal Physiology, 10.1152/ajprenal.00133.2012, 303:4, (F540-F550), Online publication date: 15-Aug-2012. Rossier B and Stutts M (2009) Activation of the Epithelial Sodium Channel (ENaC) by Serine Proteases, Annual Review of Physiology, 10.1146/annurev.physiol.010908.163108, 71:1, (361-379), Online publication date: 1-Mar-2009. Lawton W (2018) Urinary kallikrein response to acute saline or water loads in hypertensive and normal humans., Hypertension, 6:2_pt_1, (175-183), Online publication date: 1-Mar-1984. CUTHBERT A and MARGOLIUS H (2012) KININS STIMULATE NET CHLORIDE SECRETION BY THE RAT COLON, British Journal of Pharmacology, 10.1111/j.1476-5381.1982.tb09178.x, 75:4, (587-598), Online publication date: 1-Apr-1982. November 1981Vol 3, Issue 6_pt_2 Advertisement Article InformationMetrics Copyright © 1981 by American Heart Associationhttps://doi.org/10.1161/01.HYP.3.6_Pt_2.II-92 Originally publishedNovember 1, 1981 PDF download Advertisement

Acute saline expansion lowers blood pressure of early DOCA salt hypertensive rats.

Changes in blood pressure and body fluids volume caused by an acute saline load were studied in 6 normal and 7 DOCA-salt early hypertensive rats having normal inulin space and plasma volume. After loading, blood pressure increased in the normal group (+23 mm Hg) and fell (-17 mm Hg) in the DOCA-salt group. Expansion of extracellular fluid volume was similar in both groups but expansion of plasma volume was twice as high in the DOCA-salt than in the normal group. The results are compatible with an inhibition of a volume-sensitive vasopressor mechanism possibly involving vasopressin.

Role of vasopressin, catecholamines, and plasma volume in hypertonic saline-induced hypertension.

Elevation of blood pressure induced by an acute sodium and fluid load in the anephric state has been attributed to intravascular fluid volume expansion. The present experiments were designed to study the role of vasopressin and catecholamines in this type of hypertension. Normotensive anephric rats, adrenergically intact or pretreated with alpha- and beta-adrenoceptor blockade, and deoxycorticosterone (DOC)-salt-treated anephric rats, intact or pretreated with alpha- and beta-adrenoceptor blockade, received an infusion of 2 ml containing 3 meq NaCl, followed by intravenous administration of an analogue antagonist of the vasopressor effect of arginine-vasopressin (AVP). Pressure increments induced by hypertonic saline were abolished by an AVP antagonist partly in the adrenergically intact animals (leaving a small residual pressure elevation) and completely in adrenergically blocked animals, which had a larger AVP component. Volumes expansion did not necessarily accompany increase in blood pressure after saline infusion. In fact some DOC-salt-treated animals with the highest blood pressures and norepinephrine levels exhibited contraction of plasma volume. Increments in blood pressure were negatively correlated with plasma volume changes (r = -0.687, P less than 0.05) in these animals and positively with norepinephrine levels in all adrenergically intact animals (r = 0.818, P less than 0.001). It is concluded that the hypertensive response elicited by acute hypertonic saline load is due to vasoconstriction mediated partly by vasopressin and partly by the sympathetic system, which may in some way attenuate the effect of vasopressin.

Plasma substance P levels in normotensive and hypertensive subjects.

Since substance P is a potent natriuretic, diuretic, and vasodilatory peptide, a radioimmunoassay for substance P was developed, and its levels measured in the plasma of normal subjects and patients with essential hypertension. The plasma substance P levels were 186+/-14 pg/ml in normal subjects and 164+/-3 pg/ml in hypertensive patients. When the sodium content of their diet was reduced to 10 mEq/day, substance P levels failed to change, but plasma renin activity and urinary kallikrein increased. An acute saline infusion also failed to alter plasma substance P levels. Assuming an upright posture increased plasma renin activity, but not substance P, in both groups of subjects. Thus, it appears that substance P is not involved in the control of blood pressure, kallikrein excretion or renin release in man.