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.

Abstract 386: A Novel Aquaretic and Glomerular Filtration Rate Enhancing Peptide Without Vascular Vasodilatory Actions in Experimental CHF.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Horng H Chen ◽  
ShuChong Pan ◽  
John C Burnett ◽  
Robert D Simari
Keyword(s):  
Blood Pressure ◽  
Amino Acids ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urinary Sodium Excretion ◽  
Sodium Concentration ◽  
Water Excretion ◽  
Arterial Blood ◽  
Change In Mean

BACKGROUND: BNP is a cardiac peptide with vasodilatory, natriuretic and diuretic properties. Recent studies have suggested that its vasodilatory hypotensive properties may limit the renal actions of BNP, especially in patients with borderline low blood pressure. We have recently identified an alternatively spliced transcript for BNP (ASBNP) that includes a unique and distinct longer carboxyl-terminus consisting of 34 amino acids. Based upon preliminary studies, we generated a truncated form (ASBNP2.1) that contains the first 16 amino acids of the C-terminal of ASBNP. METHODS: We determined the cardiorenal and humoral actions of intravenous infusion of ASBNP2.1 at 2 pmol/Kg/min, 10 pmol/Kg/min and 100 pmol/Kg /min in 10 dogs with rapid ventricular pacing induced overt CHF (240 bpm for 10 days). * p<0.05 RESULTS: IV infusion of ASBNP 2.1 increased aquaresis (from 0.19±0.04 to 0.32±0.07, 0.46±0.11 and 0.39±0.09 ml/min*) without a significant change in urinary sodium excretion. Importantly, ASBNP 2.1 enhanced glomerular filtration rate (GFR), from 31±4 to 47±8, 69±10 and 56±9 ml/min*. These renal actions were associated with increases in urinary BNP*, ANP* and cGMP* excretion. BNP 2.1 did not have any systemic vasodilatory action resulting in no change in mean arterial blood pressure or cardiac-filling pressures even at the highest dose. There was not change in serum sodium concentration. CONCLUSION: We report for the first time that this novel peptide based upon ASBNP has potent aquaretic and GFR enhancing actions without the vasodilatory hypotensive properties in an experimental model of overt CHF. The lack of vasodilatation but with renal actions also suggest that the C-terminus plays a key role in the vascular actions of this peptide offering new insights into vascular-renal structure function of BNP and related peptides. This renal specific peptide may have potential therapeutic benefit in states of renal dysfunction with volume overload to enhance GFR and water excretion without the detrimental side effect of hypotension.

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.

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

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

1994 ◽  
Vol 7 (4 Pt 1) ◽  
pp. 308-313 ◽  
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

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.

Effect of Serotonin on Renal Hemodynamics and Sodium Excretion in the Dog

1958 ◽  
Vol 193 (3) ◽  
pp. 639-643 ◽  
Author(s):  
William P. Blackmore
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Direct Action ◽  
Renal Plasma Flow ◽  
Specific Effect ◽  
Arterial Blood ◽  
Change In Mean

The effects of constant intravenous infusion of serotonin with doses of 5 and 10 µg/kg/min. on glomerular filtration rate, effective renal plasma flow, urine flow and sodium excretion were studied in trained, unanesthetized female dogs. A small but significant decrease in glomerular filtration rate associated with increased renal plasma flow occurred at the 5 µg/kg/min. dose indicating a specific effect of serotonin on the kidney. Similar changes were noted with the 10 µg/kg/min. dose plus a marked antidiuretic effect that occurred in the absence of any significant change in mean arterial blood pressure and an intact neurohypophysis indicating a direct action on water reabsorption in the kidney. Urinary sodium excretion decreased with both doses as a result of a decline in glomerular filtration rate associated with increased tubular reabsorption. These results indicate that serotonin has a specific effect on the kidney and suggest that this substance may alter the caliber of the glomerular vessels to decrease renal vascular resistance.

Peripheral Haemodynamics and Renal Function in Relation to the Menstrual Cycle

1996 ◽  
Vol 91 (2) ◽  
pp. 163-168 ◽  
Author(s):  
E. Van Beek ◽  
A. J. H. M. Houben ◽  
P. N. Van Es ◽  
C. Willekes ◽  
E. C. C. M. Korten ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Menstrual Cycle ◽  
Glomerular Filtration ◽  
Luteal Phase ◽  
Filtration Rate ◽  
Vascular Tone ◽  
Vascular Relaxation ◽  
Arterial Blood

1. The objective of this study was to investigate whether the luteal phase of the menstrual cycle differs from the follicular phase by the development of a state of general vascular relaxation. 2. Once in the follicular and once in the luteal phase of the menstrual cycle, we measured by non-invasive techniques: arterial blood pressure (by finger blood pressure measurements), vascular tone (by pulse-wave velocity and plethysmography), blood flow to skin (by laser-Doppler), blood flow to forearm (by plethysmography) and blood flow to kidneys (by para-aminohippurate clearance), and the glomerular filtration rate (by inulin clearance). The data points obtained in the luteal phase were compared with those in the follicular phase by non-parametric tests. 3. Arterial blood pressure, vascular tone and the blood flows to the forearm and kidneys were comparable in the two phases of the menstrual cycle. In contrast, the blood flow to the skin was consistently lower, and the glomerular filtration rate higher in the luteal phase of the menstrual cycle. 4. The results of the present study do not support our hypothesis of a general vascular relaxation in the luteal phase of the menstrual cycle. The lower skin flow in the luteal phase may be an adaptation needed to ensure the higher core temperature of 0.3–0.5°C in the luteal phase. The higher glomerular filtration rate was in most cases paralleled by a higher renal blood flow in the luteal phase. This suggests that the higher glomerular filtration rate is secondary to a selective vasorelaxation of the afferent renal arterioles.

The Effects of Vandellia Cordifolia on Renal Functions and Arterial Blood Pressure

1989 ◽  
Vol 17 (03n04) ◽  
pp. 203-210
Author(s):  
Huei-Yann Tsai ◽  
Ruey-Tean Chiang ◽  
Tzu-Wei Tan ◽  
Ho-Chan Chen
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Renal Tubules ◽  
Diuretic Effect ◽  
Renal Functions ◽  
Arterial Blood

Vandellia cordifolia (COLSM) G, DON of Scrophulariaceae (V. cordifolia) is an annual wild herb indigenous to Taiwan. It can be found in plains, low altitudes, swampy places, and paddy fields. Taiwanese folk physicians use it in "nephritis, uremia, furnucle, carbuncle." The LD50 (95% confidence limit) of the crude exract of V. codifolia given by the oral route was more than 10 g/kg in rats. By the intraperitoneal route, it was 4.6 g/kg (4.35–4.93), The extraction rate was 16.6%. We studied its effects on renal functions and blood pressure and found that (1) it had diuretic effect on normal rats, (2) it decreased glomerular filtration rate and renal blood flow on normal kidneys in rabbits, (3) it had no effects on glomerular filtration rate and renal blood flow on glycerin-induced insufficient kidneys in rabbits, (4) it had diuretic effects on both normal and glycerin-induced insufficient kidneys in rabbits, (5) it could inhibit Na+ and K+ reabsorptionn on normal and glycerin-induced insufficient kidneys in rabbits, (6) it had hypertensive effect and this effect could be blocked by phenoxybenzamine. From the above facts, we conclude that V, cordifolia had diuretic effect and it may act on renal tubules to inhibit Na+ and K+ reabsorption.

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