Amiloride-sensitive lithium reabsorption during doxazosin-induced blood pressure reduction in rats

1991 ◽  
Vol 81 (6) ◽  
pp. 809-814 ◽  
Author(s):  
Jørgen Søberg Petersen ◽  
Michael Shalmi ◽  
Martin Bak ◽  
Niels Lomholt ◽  
Sten Christensen
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Mean Arterial Blood Pressure ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Excretion Rate ◽  
Urine Flow ◽  
Lithium Clearance ◽  
Arterial Blood

1. The effects of acute systemic α1-anoceptor blockade by doxazosin on glomerular filtration rate, urine flow, sodium clearance and lithium clearance were investigated in acutely prepared conscious rats. 2. Clearance experiments were performed during water diuresis (20 mmol/l NaCl and 110 mmol/l glucose, 3 ml/h). After a control period, animals were randomized to one of the following treatments: time-control (n = 9), doxazosin (50 μg primer; 30 μg h−1 kg−1) (n = 10), amiloride (1 mg primer; 2.4 mg h−1 kg−1) (n = 10) and doxazosin plus amiloride (n = 9). 3. Doxazosin reduced the mean arterial blood pressure from 125 to 108 mmHg; this was associated with transient reductions in glomerular filtration rate, urine flow and lithium clearance. After the transient anti-diuresis, the sodium excretion rate remained reduced in doxazosin-infused animals. Amiloride increased the sodium excretion rate without having effects on other variables. When doxazosin was given together with amiloride, the reduction in lithium clearance observed during the transient reduction in glomerular filtration rate and urine flow, was partly abolished. Thus the fractional lithium excretion was transiently increased in rats given doxazosin plus amiloride (from 29 to 40%), whereas in rats given doxazosin alone a non-significant reduction was observed (from 28 to 25%). The dissociation between lithium clearance and fractional lithium excretion in the two doxazosin-infused groups was only significant during the transient reduction in glomerular filtration rate and urine flow. 4. The results provide evidence for an amiloride-sensitive lithium reabsorption during acute systemic α1-adrenoceptor blockade. It is suggested that activation of baroreflexes during the acute reduction in mean arterial blood pressure is responsible for stimulation of distal lithium reabsorption by an unknown mechanism.

Angiotensin-(1–7) in the ovine fetus

2001 ◽  
Vol 280 (2) ◽  
pp. R404-R409 ◽  
Author(s):  
Karen M. Moritz ◽  
Duncan J. Campbell ◽  
E. Marelyn Wintour
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Flow Rate ◽  
Filtration Rate ◽  
Plasma Concentrations ◽  
Urine Flow ◽  
Urine Flow Rate ◽  
Ang Ii ◽  
Arterial Blood

In the adult animal, ANG-(1–7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1–7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers ( n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1–7), and ANG II were 86 ± 21, 13 ± 2, and 14 ± 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 ± 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1–7) (2.9 ± 0.6 fmol/ml), whereas ANG II concentrations were not different (10 ± 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 ± 1.1 pmol ANG I · ml−1 · h−1) than in the ewe (0.9 ± 0.2 pmol · ml−1 · h−1, P < 0.05). Infusion of ANG-(1–7) (∼9 μg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1–7) reaching a maximum of 448 ± 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days ( n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1–7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT1 receptor, and AT2 receptor were elevated in kidneys of fetuses that received infusions of ANG-(1–7). Infusion of an ANG-(1–7) antagonist {[d-Ala7]-ANG-(1–7), 20 μg/h} for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1–7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1–7) may play a role in the fetal kidney.

Effects of small C-ANF receptor ligands on plasma levels of atrial natriuretic factor, blood pressure, and renal function in the rat

1991 ◽  
Vol 69 (10) ◽  
pp. 1561-1566 ◽  
Author(s):  
Juraj Okolicany ◽  
Glenn A. McEnroe ◽  
Lisa C. Gregory ◽  
John A. Lewicki ◽  
Thomas Maack
Keyword(s):  
Blood Pressure ◽  
Amino Acids ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Levels ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Recovery Period ◽  
Receptor Ligands ◽  
Arterial Blood

In this article, after a very brief review on ANF receptors, we report our study on the effects of small C-ANF receptor ligands in the rat. Two small ligands were synthesized: 2-napthoxyacetyl-isonipecotyl-rANF 11–15-NH2 (5 aa), containing 5 amino acids; and Ala7-rANF 8–17-NH2 (10 aa), containing 10 amino acids from the ring structure of ANF 1–28. After control periods, 5 aa or 10 aa were infused i.v. at a dose of 10 μg∙min−1∙kg−1 body weight for 70 min in anesthetized rats, followed by a 60-min recovery period. The 5 aa and 10 aa peptides significantly and reversibly increased plasma levels of endogenous immunoreactive ANF by 106 ± 29 and 52 ± 24 pg/mL, respectively. Infusion of the 5 aa peptide significantly decreased mean arterial blood pressure from 113 ± 1 to 100 ± 3 mmHg (1 mmHg = 133.32 Pa) and increased glomerular filtration rate from 1.6 ± 0.2 to 2.3 ± 0.2 mL/min, sodium excretion from 0.6 ± 0.3 to 3.4 ± 0.4 μmol/min, and potassium excretion from 0.5 ± 0.2 to 1.2 ± 0.2 μmol/min. Similar results were obtained with the 10 aa peptide. The effects of both peptides on blood pressure and sodium excretion persisted throughout the recovery period. The results confirm and extend previous observations showing that C-ANF receptors mediate the removal of ANF from the circulation. The shortening of the minimal peptide length necessary to bind to C-ANF receptors markedly enhances the possibility of developing orally active C-ANF receptor ligands for the treatment of cardiovascular and renal diseases.Key words: C-ANF receptors, linear atrial peptides, glomerular filtration rate, natriuresis, kaliuresis.

Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

1999 ◽  
Vol 276 (3) ◽  
pp. R684-R695 ◽  
Author(s):  
Morten Heiberg Bestle ◽  
Niels Vidiendal Olsen ◽  
Poul Christensen ◽  
Benny Vittrup Jensen ◽  
Peter Bie
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Glomerular Filtration Rate ◽  
Stroke Volume ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Excretion Rate ◽  
Renal Tubules ◽  
Arterial Blood

Effects of urodilatin (5, 10, 20, and 40 ng ⋅ kg−1⋅ min−1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13–37%) and increased fractional Li+clearance (7–22%) and urinary Na+excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng ⋅ kg−1⋅ min−1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood pressure and heart rate. The two highest doses elicited larger decreases in stroke volume (17 and 21%) but also decreased blood pressure (6 and 14%) and increased heart rate (15 and 38%), such that cardiac output remained unchanged. Hematocrit and plasma protein concentration increased with the three highest doses. The renin-angiotensin-aldosterone system was inhibited by the three lowest doses but activated by the hypotensive dose of 40 ng ⋅ kg−1⋅ min−1. Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreactivity (including urodilatin) and plasma cGMP increased dose dependently. The urinary excretion rate of albumin was elevated up to 15-fold (37 ± 17 μg/min). Use of a newly developed assay revealed that baseline urinary urodilatin excretion rate was low (<10 pg/min) and that fractional excretion of urodilatin remained below 0.1%. The results indicate that even moderately natriuretic doses of urodilatin exert protracted effects on systemic hemodynamic, endocrine, and renal functions, including decreases in cardiac output and renal blood flow, without changes in arterial pressure or glomerular filtration rate, and that filtered urodilatin is almost completely removed by the renal tubules.

Effect of Urodilatin Infusion on Renal Haemodynamics, Tubular Function and Vasoactive Hormones

1997 ◽  
Vol 92 (4) ◽  
pp. 397-407 ◽  
Author(s):  
JAN Carstens ◽  
Kaare T. Jensen ◽  
Erling B. Pedersen
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Part ◽  
Renal Haemodynamics ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Short Term

1. The renal efficacy of urodilatin in humans has only been partly investigated. It is unknown whether intravenously infused urodilatin has an effect on sodium reabsorption in both the proximal and distal part of the nephron. 2. Twelve healthy subjects participated in this double-blind, placebo-controlled study in a crossover design. They received, in a randomized order, a short term (60 min) infusion of urodilatin in three different doses (10, 20 and 40 ng min−1 kg−1 of body weight) and placebo. Renal haemodynamics were estimated by clearance technique with radioactive tracers, and proximal tubular handling of sodium was evaluated by lithium clearance. 3. The 20 ng min−1 kg−1 dose increased the urinary sodium excretion and urinary flow rate compared with the effects of placebo. It increased the glomerular filtration rate and decreased the effective renal plasma flow. In addition, the dose increased the lithium clearance compared with placebo, but did not significantly change the fractional excretion of lithium. On the other hand, it markedly decreased the distal fractional reabsorption of sodium. It also had a suppressive effect on renin secretion. The systemic arterial blood pressure was unchanged, but the dose increased the pulse rate and the haematocrit. The highest dose (40 ng min−1 kg−1) induced a wide variation in the natriuretic and diuretic responses, probably due to a blood-pressure-lowering effect. 4. We conclude, that the urodilatin dose of 20 ng min−1 kg−1 of body weight was most efficacious in this short-term infusion study, and that it had potent natriuretic and diuretic qualities, probably due to stimulation of the glomerular filtration rate and inhibition of sodium reabsorption in the distal part of the nephron.

Meclofenamate and urine concentration with and without exposure of the renal papilla

1981 ◽  
Vol 240 (5) ◽  
pp. F423-F429 ◽  
Author(s):  
R. J. Roman ◽  
C. Lechene
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Prostaglandin Synthesis ◽  
Urine Flow ◽  
Renal Papilla ◽  
Arterial Blood ◽  
Pelvic Urine

The recent finding that inhibitors of prostaglandin synthesis prevent the fall in urine concentration produced by papillary exposure challenges the hypothesis that contact between the pelvic urine and papilla is essential to the renal concentrating process. The present study examines the change in urine osmolality produced by exposure of the renal papilla in rats given meclofenamate. In control animals urine osmolality(Uosmol) decreased 57% after 2 h of exposure of the renal papilla. In rats given meclofenamate 4 mg/kg urine osmolality increased 16%, urine flow decreased 30%, and glomerular filtration rate was unchanged in the nonexposed kidney. Meclofenamate, however, did not alter the decrease in Uosmol seen in the kidney with the exposed papilla. Meclofenamate 10 mg/kg was also ineffective in preventing the fall in urine osmolality produced by papillary exposure, although this higher dose decreased glomerular filtration rate and arterial blood pressure. These results are consistent with the finding that pelvic urine urea is important to the urinary concentrating process and with the hypothesis that urine osmolality falls after papillary exposure because contact between pelvic urine and papilla is interrupted.

Renal and hemodynamic effects of losartan in conscious dogs during controlled mechanical ventilation

1999 ◽  
Vol 276 (3) ◽  
pp. F425-F432 ◽  
Author(s):  
Martin O. Krebs ◽  
Thorsten Kröhn ◽  
Willehad Boemke ◽  
Rainer Mohnhaupt ◽  
Gabriele Kaczmarczyk
Keyword(s):  
Mechanical Ventilation ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Urine Volume ◽  
Conscious Dogs ◽  
Positive End Expiratory Pressure ◽  
Arterial Blood ◽  
Controlled Mechanical Ventilation

In 12 conscious dogs, we investigated whether the angiotensin II-receptor antagonist losartan increases renal sodium excretion and urine volume during controlled mechanical ventilation (CMV) with positive end-expiratory pressure. In four experimental protocols, the dogs were extracellular volume (ECV) expanded (electrolyte solution, 0.5 ml ⋅ kg−1 ⋅ min−1iv) or not and received losartan (100 μg ⋅ kg−1 ⋅ min−1iv) or not. They breathed spontaneously during the 1st and 4th hour and received CMV with positive end-expiratory pressure (mean airway pressure 20 cmH2O) during the 2nd and 3rd hours. In the expansion group, dogs with losartan excreted ∼18% more sodium (69 ± 7 vs. 38 ± 5 μmol ⋅ min−1 ⋅ kg−1) and 15% more urine during the 2 h of CMV because of a higher glomerular filtration rate (5.3 ± 0.3 vs. 4.5 ± 0.2 ml ⋅ min−1 ⋅ kg−1) and the tubular effects of losartan. In the group without expansion, sodium excretion (2.0 ± 0.6 vs. 2.6 ± 1.0 μmol ⋅ min−1 ⋅ kg−1) and glomerular filtration rate (3.8 ± 0.3 vs. 3.8 ± 0.4 ml ⋅ min−1 ⋅ kg−1) did not change, and urine volume decreased similarly in both groups during CMV. Plasma vasopressin and aldosterone increased in both groups, and plasma renin activity increased from 4.9 ± 0.7 to 7.8 ± 1.3 ng ANG I ⋅ ml−1 ⋅ h−1during CMV in nonexpanded dogs without losartan. Mean arterial pressure decreased by 10 mmHg in nonexpanded dogs with losartan. In conclusion, losartan increases sodium excretion and urine volume during CMV if the ECV is expanded. If the ECV is not expanded, a decrease in mean arterial blood pressure and/or an increase in aldosterone and vasopressin during CMV attenuates the renal effects of losartan.

Short-term analysis of the relationship between blood pressure and urinary sodium excretion in normotensive subjects

2000 ◽  
Vol 98 (4) ◽  
pp. 495-500 ◽  
Author(s):  
Leonardo CENTONZA ◽  
Giovanna CASTOLDI ◽  
Roberto CHIANCA ◽  
Giuseppe BUSCA ◽  
Raffaello GOLIN ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Short Term ◽  
Quiet Wakefulness ◽  
Normotensive Subjects

The aim of this study was to investigate whether, in the short term, physiological blood pressure changes are coupled with changes in urinary sodium excretion in normotensive subjects, maintained at fixed sodium intake and under controlled postural and behavioural conditions. Twelve normotensive subjects were recruited. For each subject, seven urine samples were collected at fixed time intervals during an overall 26 h period: late afternoon (16.00–20.00 hours), evening (20.00–24.00 hours), night (24.00–06.00 hours), quiet wakefulness (06.00–09.00 hours), morning (09.00–12.00 hours), post-prandial (12.00–15.00 hours) and afternoon (15.00–18.00 hours). Blood pressure was monitored by an ambulatory blood pressure device during the whole 26 h period. Each urine sample was used to measure urinary sodium excretion and glomerular filtration rate (creatinine clearance). Blood pressure, heart rate, urinary sodium excretion and glomerular filtration rate recorded in the daytime were higher than those measured during the night-time. A significant positive correlation between mean blood pressure and urinary sodium excretion was found during the night, over the whole 26 h period, and during two subperiods of the daytime: quiet wakefulness and the post-prandial period. The coefficient of the pressure–natriuresis curve was significantly decreased by postural changes. We conclude that, in normotensive subjects, blood pressure and urinary sodium excretion are coupled in the short term. The assumption of an upright posture can mask this relationship, presumably by activating neurohumoral factors.

The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate

2015 ◽  
Vol 214 (4) ◽  
pp. 497-510 ◽  
Author(s):  
M. Damkjaer ◽  
T. Wang ◽  
E. Brøndum ◽  
K. H. Østergaard ◽  
U. Baandrup ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Arterial Blood Pressure ◽  
Filtration Rate ◽  
Interstitial Pressure ◽  
Arterial Blood

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

1987 ◽  
Vol 65 (11) ◽  
pp. 2219-2224 ◽  
Author(s):  
J. Krayacich ◽  
R. L. Kline ◽  
P. F. Mercer
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Fractional Excretion Of Sodium ◽  
Infusion Of Norepinephrine

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 μg/min, i.v.), an α1 adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (−67 ± 9 vs. −33 ± 8%), glomerular filtration rate (−60 ± 9 vs. −7 ± 20%), urine flow (−61 ± 7 vs. −24 ± 11%), sodium excretion (−51 ± 15 vs. −32 ± 21%), and fractional excretion of sodium (−50 ± 9 vs. −25 ± 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (−54 ± 10 vs. −30 ± 14%), glomerular filtration rate (−51 ± 11 vs. −19 ± 17%), urine flow (−55 ± 10 vs. −39 ± 10%), sodium excretion (−70 ± 9 vs. −59 ± 11%), and fractional excretion of sodium (−53 ± 10 vs. −41 ± 10%). These results suggest that vascular and tubular supersensitivity to norepinephrine in chronically denervated kidneys is due to postsynaptic changes involving α1-adrenergic receptors.

Sign in / Sign up

Export Citation Format

Share Document