Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats

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.

Download Full-text

Endothelin Excretion in Hypertensive Pregnancy: Relationship to Glomerular Filtration Rate, Blood Pressure, and Sodium Excretion

American Journal of Hypertension ◽

10.1093/ajh/7.4.308 ◽

1994 ◽

Vol 7 (4 Pt 1) ◽

pp. 308-313 ◽

Cited By ~ 16

Author(s):

M.-X. Wang ◽

M. A. Brown ◽

M. L. Buddie ◽

M. A. Carlton ◽

G. M. Cario ◽

...

Keyword(s):

Blood Pressure ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Sodium Excretion ◽

Filtration Rate ◽

Hypertensive Pregnancy

Download Full-text

Natriuresis Following Fourth Ventricle Perfusion with High-sodium Artificial CSF

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y75-052 ◽

1975 ◽

Vol 53 (3) ◽

pp. 363-367 ◽

Cited By ~ 10

Author(s):

S. S. Passo ◽

J. R. Thornborough ◽

A. B. Rothballer

Keyword(s):

Blood Pressure ◽

Cerebrospinal Fluid ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Sodium Excretion ◽

Fourth Ventricle ◽

Filtration Rate ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

High Sodium

Perfusion of the fourth cerebral ventricle with high-sodium artificial cerebrospinal fluid was found to result in an increase in urinary sodium excretion in anesthetized cats. The natriuresis was accompanied by an increase in blood pressure and glomerular filtration rate. However, in animals with the changes in blood pressure and glomerular filtration rate prevented by alpha-adrenergic blockade (phenoxybenzamine), the increase in urinary sodium excretion persisted. The data suggest the presence of a neural mechanism in the vicinity of the fourth ventricle sensitive to cerebrospinal fluid sodium levels and capable of affecting urinary sodium excretion independent of changes in blood pressure or glomerular filtration rate. The possible role of the area postrema and adjacent medulla is considered.

Download Full-text

Effect of a kinin antagonist on renal function and haemodynamics during alterations in sodium balance in conscious normotensive rats

Clinical Science ◽

10.1042/cs0780165 ◽

1990 ◽

Vol 78 (2) ◽

pp. 165-168 ◽

Cited By ~ 6

Author(s):

Paolo Madeddu ◽

Nicola Glorioso ◽

Aldo Soro ◽

Paolo Manunta ◽

Chiara Troffa ◽

...

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Renal Blood Flow ◽

Sodium Excretion ◽

Filtration Rate ◽

Sodium Intake ◽

Urinary Sodium Excretion

1. To evaluate whether sodium intake can modulate the action of endogenous kinins on renal function and haemodynamics, a receptor antagonist of bradykinin was infused in conscious normotensive rats maintained on either a normal or a low sodium diet. 2. The antagonist inhibited the hypotensive effect of exogenously administered bradykinin. It did not change the vasodepressor effect of acetylcholine, dopamine or prostaglandin E2. 3. The antagonist did not affect mean blood pressure, glomerular filtration rate, renal blood flow or urinary sodium excretion, in rats on sodium restriction. It did not change mean blood pressure, glomerular filtration rate or urinary sodium excretion, but decreased renal blood flow, in rats on a normal sodium intake. 4. The kallikrein–kinin system has a role in the regulation of renal blood flow in rats on a normal sodium diet.

Download Full-text

CNS-induced natriuresis and renal hemodynamics in conscious rats

AJP Renal Physiology ◽

10.1152/ajprenal.1983.245.6.f763 ◽

1983 ◽

Vol 245 (6) ◽

pp. F763-F771 ◽

Cited By ~ 1

Author(s):

D. Beasley ◽

R. L. Malvin ◽

D. R. Mouw

Keyword(s):

Blood Pressure ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Antidiuretic Hormone ◽

Sodium Excretion ◽

Filtration Rate ◽

Plasma Renin ◽

Renal Nerve ◽

Natriuretic Hormone ◽

Renal Nerve Activity

Sodium excretion was studied following experimental elevation of cerebrospinal fluid (CSF) sodium in heterozygous and homozygous (DI) Brattleboro rats given exogeneous antidiuretic hormone. Sodium excretion increased 4.5-fold in heterozygous and 3.5-fold in DI rats. The natriuresis in both groups was rapid in onset and occurred with a simultaneous kaliuresis. Blood pressure increased approximately 10 mmHg in the heterozygous but not in the DI rats. Accordingly, increased blood pressure may contribute to the natriuresis but is not the sole mechanism. Plasma renin concentration did not change in the DI rats during high Na CSF infusion, and chronic bilateral renal denervation did not abolish the natriuresis. Glomerular filtration rate increased during the high Na period in both the intact and renally denervated rats. These data provide evidence that a natriuretic mechanism exists that is not mediated by changes in antidiuretic hormone, renal nerve activity, mean arterial pressure, aldosterone, or angiotensin II, and thus may be due to another circulating substance or natriuretic hormone. This hormone may act totally or in part by increasing glomerular filtration rate.

Download Full-text

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-232 ◽

1991 ◽

Vol 69 (10) ◽

pp. 1561-1566 ◽

Cited By ~ 4

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.

Download Full-text

Knockout of Macula Densa Neuronal Nitric Oxide Synthase Increases Blood Pressure in db/db Mice

Hypertension ◽

10.1161/hypertensionaha.121.17643 ◽

2021 ◽

Author(s):

Jie Zhang ◽

Ximing Wang ◽

Yu Cui ◽

Shan Jiang ◽

Jin Wei ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Sodium Excretion ◽

Filtration Rate ◽

Leptin Receptor ◽

Macula Densa ◽

Glomerular Hyperfiltration ◽

No Production

Hypertension is a common comorbid condition in patients with diabetes. The pathogenesis of hypertension in diabetes has not been fully clarified. Primary tubular hyperreabsorption may contribute, which may be counteracted by glomerular hyperfiltration in the early diabetic kidney. In this study, we hypothesize that in early diabetes, the macula densa neuronal nitric oxide synthase (NOS1)-derived nitric oxide (NO) production is enhanced, which blunts tubuloglomerular feedback (TGF) response, promotes glomerular hyperfiltration, and maintains normal blood pressure; conversely, insufficient NO generation by the macula densa induces hypertension by lowering glomerular filtration rate and thus inhibiting natriuresis. To test this hypothesis, we examined the changes of macula densa NOS1 expression and phosphorylation as well as NO production, TGF response, glomerular filtration rate, sodium excretion, and blood pressure in a murine model of leptin receptor-deficient (db/db) diabetes with or without macula densa-specific NOS1 deletion. We found that db/db mice presented reduced fractional renal sodium excretion and only a small increase in blood pressure, associated with upregulated expression and activity of macula densa NOS1, inhibited TGF response, and glomerular hyperfiltration. Genetic knockout of macula densa NOS1 restored the TGF response and attenuated glomerular hyperfiltration in db/db mice but also further reduced fractional renal sodium excretion and substantially increased blood pressure. In conclusion, the present study demonstrates that in the early stage of leptin receptor-deficient diabetes, the upregulation of macula densa NOS1 inhibits TGF and increases glomerular filtration rate, which counteracts renal sodium retention and limits the rise in blood pressure.

Download Full-text