Effect of atrial natriuretic factor in rat pregnancy

1986 ◽  
Vol 250 (4) ◽  
pp. R589-R594 ◽  
Author(s):  
C. G. Kristensen ◽  
Y. Nakagawa ◽  
F. L. Coe ◽  
M. D. Lindheimer

Protocols were designed to 1) identify atrial natriuretic factor (ANF) bioactivity in pregnant rats, 2) compare ANF activity in atria from gravid and virgin Sprague-Dawley animals, and 3) assess renal and vascular responsiveness to ANF during gestation. Similar quantities of ANF were extracted from atria of term gravid and age-matched controls (assayed as the natriuretic response in awake virgins). We then purified by high-performance liquid chromatography a peptide identical to the synthetic 23 amino acid atriopeptin II (AP II). With equimolar injections of ANF, gravid rats had a blunted natriuretic response (P less than 0.05). However, when dose was based on estimated extracellular volume, awake virgin and pregnant animals displayed similar highly significant dose-response curves to infused AP II (R's 0.8). When hydropenic rats were assayed, both gravid and virgins required 10 times more ANF to initiate a diuresis; dose-response curves again being similar and highly significant. Decrements in blood pressure were also similar in pregnant and nongravid animals. Thus, despite an increased intravascular volume of 70% during gestation, cardiac content of ANF and the renal and vascular responsiveness to this peptide are similar to those in virgin rats, suggesting resetting of ANF-volume relationships during pregnancy.

1995 ◽  
Vol 268 (3) ◽  
pp. F416-F422 ◽  
Author(s):  
S. Omer ◽  
S. Mulay ◽  
P. Cernacek ◽  
D. R. Varma

The influence of pregnancy on renal responses to atrial natriuretic factor (ANF) was determined in urethane-anesthetized Sprague-Dawley rats. Infusions of ANF caused a significantly greater increase in urinary excretion of fluid, sodium, and potassium in virgin than in pregnant (13-15 days and 21 days) rats. Guanosine 3',5'-cyclic monophosphate (cGMP) excretion, mean arterial pressure, plasma immunoreactive ANF, and glomerular filtration rate (GFR) following ANF infusions were not different in virgin and gravid rats, although increments in GFR over basal were greater in virgin than in gravid animals. Renal responses to ANF normalized during postpartum and were attenuated by progesterone treatment of virgin rats. Natriuretic effects of infusions of ANF plus ANF-(4-23) (a ligand for clearance receptors) or of ANF plus thiorphan (an endopeptidase inhibitor) in virgin and pregnant rats did not differ; ANF-(4--23) and thiorphan alone caused greater natriuresis in pregnant than in virgin rats. Effects of ANF on cGMP production by collecting duct cells isolated from virgin and pregnant rats did not differ. We concluded that the attenuation in the renal effects of ANF during pregnancy might be mediated by progesterone by an increase in the intrarenal metabolism of ANF and might reflect physiological adjustment to facilitate fluid/electrolyte expansion.


1987 ◽  
Vol 253 (5) ◽  
pp. F917-F928 ◽  
Author(s):  
M. Suzuki ◽  
F. A. Almeida ◽  
D. R. Nussenzveig ◽  
D. Sawyer ◽  
T. Maack

A new methodological approach was developed to study the relationship between specific binding and dose-response curves of the renal effects of atrial natriuretic factor (ANF) in isolated perfused rat kidneys (IK). IK were perfused with 125I-labeled and unlabeled ANF 1-28 (4 pM to 1 microM) to determine the following: 1) distribution, capacity (Cmax), and apparent affinity (S50) of specific binding of ANF 1-28 in cortex, outer medulla, and papilla and 2) dose-response curves of the effects of ANF 1-28 on renal hemodynamics and excretion of fluid and electrolytes. The kidney had a very high density of high-affinity binding sites for ANF. Cortex had greater than 90% of total binding sites (Cmax = 6.8 pmol/g tissue; S50 = 54 pM), whereas papilla had less than 2% of total binding sites with a 10-fold lower apparent affinity (S50 = 860 pM) than in cortex. ANF-induced increases in glomerular filtration rate and excretion of fluid and electrolytes were detectable at 10-100 pM and maximal effects occurred at 1-10 nM ANF. Below 1 nM there was no dissociation between the renal hemodynamic and natriuretic effects of ANF. There was a close agreement between dose-response and binding curves of ANF to cortex. Results demonstrate that binding site occupancy in kidney cortex and renal effects of ANF occur at near physiological concentrations of the hormone.


1990 ◽  
Vol 258 (3) ◽  
pp. F741-F750 ◽  
Author(s):  
B. H. Yuan ◽  
J. B. Robinette ◽  
J. D. Conger

Differential sensitivity of the pre- and postglomerular arterial vessels to vasoconstrictor activity of angiotensin II (ANG II) and norepinephrine (NE) is controversial. To avoid the complex extravascular neurohumoral variables that may have accounted for different results in the intact rat kidney, an isolated arteriole technique was used to examine the dose responses of ANG II and NE on afferent (AA) and efferent arterioles (EA) from Sprague-Dawley rats. EA were more sensitive than AA to ANG II (EC50 = 3.2 +/- 1.8 x 10(-11) and 1.0 +/- 1.6 x 10(-9) M, respectively, P less than 0.001), whereas EC50 of both AA and EA to NE were similar (3.4 +/- 2.3 x 10(-8) and 1.4 +/- 2.6 x 10(-8) M, respectively). The dose-response curves of AA to ANG II were not different when perfused at different luminal pressures (90 and 30 mmHg). In contrast, EA were more sensitive to ANG II at 30 than at 90 mmHg (3.0 +/- 1.2 x 10(-11) and 5.0 +/- 1.8 x 10(-10) M, respectively, P less than 0.005). The EC50 of EA to NE was unaffected by similar changes in luminal pressures. The mean dose-response curves of AA to ANG II were the same with and without the addition of 10(-5) M indomethacin; however, in arterioles displaying a focal constriction pattern to ANG II the response became uniform. It is concluded that, in the isolated rat glomerular arterioles, EA are more sensitive to ANG II than AA, but both vessels respond similarly to NE. The decreased ANG II sensitivity in AA is not related to the higher in vivo pressure, and the attenuated response in AA does not appear to be mediated primarily through ANG II-stimulated vasodilator prostanoid activity. EA sensitivity to ANG II appears to be inversely related to lumen pressure.


1991 ◽  
Vol 69 (8) ◽  
pp. 1155-1162 ◽  
Author(s):  
Gordon Bolger ◽  
Francine Liard ◽  
Richard Krogsrud ◽  
Ewald Welchner ◽  
Jorge Jaramillo

The potential interaction (s) between atrial natriuretic factor (ANF) and porcine–human endothelin (ET-1) was investigated in the endothelium-denuded rat aortic ring preparation. ET-1 produced a sustained contraction of aortic rings with an ED50 of 3.6 ± 0.49 × 10−9 M. Within the concentration range of 10−9 to 10−7 M, both rat ANF 103–126 and rat ANF 99–126 when preincubated with tissues reduced the contractile efficacy of ET-1 especially at low concentrations resulting in a small but significant rightward shift of the dose–response curve to ET-1. In contrast, at a concentration of 10−10 M, rANF 99–126 but not rANF 103–126 produced a significant leftward shift of the dose–response curve to ET-1 and an increase in the maximal developed tension for the dose–response curve to ET-1. For tissues incubated in the absence of extracellular calcium or in the presence of the calcium channel blocker nifedipine (5 × 10−7 M), both ANF derivatives produced a dose-dependent decrease in the maximum contraction, but no change in potency to ET-1. Addition of either rANF 103–126 or rANF 99–126 to tissues maximally contracted with ET-1 resulted in relaxation, reaching a maximum of 70%. The ED50 values for relaxation were 2.7 ± 0.51 × 10−8 and 3.5 ± 0.60 ± 10−8 M for rANF 103–126 and rANF 99–126, respectively. ET-1 did not interact with biologically responsive and clearance receptors for ANF. These results suggest that the major circulating form of ANF may act as a physiologic antagonist of endogenous ET-1 primarily affecting the intracellular calcium-dependent component of contraction to ET-1.Key words: endothelin, atrial natriuretic factor, rat aortic ring, contraction, relaxation.


1990 ◽  
Vol 68 (3) ◽  
pp. 425-430 ◽  
Author(s):  
Kaushik P. Patel ◽  
Ping L. Zhang

To determine whether the renal responses to atrial natriuretic factor (ANF) are altered in the diabetic state, the diuretic and natriuretic responses to ANF (0.25 μg∙kg−1∙min−1, i.v.) were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Urine flow and sodium excretion were measured before and after ANF from innervated and denervated kidneys in anesthetized (Inactin 0.1 g/kg, i.p.) control and DIA rats (Sprague–Dawley rats injected with vehicle or STZ 65 mg/kg, i.p., respectively, 2 weeks prior to the experiment). Blood glucose levels were significantly elevated in the DIA group compared with the control group. ANF produced a significantly blunted diuresis and natriuresis in DIA rats compared with control rats. In addition, reducing the hyperglycemia in DIA rats by treatment with insulin (third group) reversed the blunted urine flow and sodium excretion responses to ANF. This study demonstrates that (i) there is a blunted natriuresis and diuresis to ANF in the STZ-induced DIA rats, and (ii) restoring the glucose levels to normal by insulin treatment in the DIA rats normalized the renal responses to ANF.Key words: diuresis, natriuresis, renal nerves, atrial natriuretic factor.


1995 ◽  
Vol 73 (1) ◽  
pp. 140-144 ◽  
Author(s):  
Shree Mulay ◽  
Patrice Vaillancourt ◽  
Saeed Omer ◽  
Daya R. Varma

We recently reported that the hormonal status of female rats modified atrial natriuretic factor (ANF) receptors and the aldosterone-suppressant activity of ANF in adrenal glomerulosa cells; here we investigated if this was also true for adrenal fasciculata cells. Adrenal fasciculata cells from animals in different hormonal states contained guanylate cyclase linked ANF-R1 receptors but not ANF-R2 (clearance) receptors. The concentration of ANF-R1 receptors in cells from intact virgin rats was insignificantly higher than in cells from 13- to 15-day pregnant rats and significantly higher than in cells from ovariectomized (OVX), OVX β-estradiol-treated, and OVX progesterone-treated rats. Under none of the hormonal states did ANF suppress adrenocorticotropic hormone (ACTH) stimulated corticosterone secretion. Data suggest that the interactions between ANF and ACTH on mineralocorticoid and glucocorticoid synthesis markedly differ.Key words: atrial natriuretic factor receptors, corticosterone, estrogen, progesterone, pregnancy.


1986 ◽  
Vol 251 (4) ◽  
pp. E497-E501 ◽  
Author(s):  
P. Januszewicz ◽  
G. Thibault ◽  
J. Gutkowska ◽  
R. Garcia ◽  
C. Mercure ◽  
...  

To determine the effect of water deprivation (mixed volume and osmotic stimulus) on the secretion of atrial natriuretic factor (ANF) and arginine vasopressin (AVP), plasma immunoreactive ANF (IR-ANF), and plasma AVP were measured in normal conscious Sprague-Dawley rats. IR-ANF was decreased to 19.9 +/- 3.6 pg/ml (24 h dehydration), 9.8 +/- 2.5 pg/ml (48 h dehydration), and undetectable level (72 h dehydration) from the control level of 62.4 +/- 2.4 pg/ml. These decreases were accompanied by significant increase in plasma AVP, serum Na+, osmolality (osm), and hematocrit (Hct). In animals deprived of water for 3 days the secretion of ANF and AVP was monitored at seven time points during the 1st h after voluntary rehydration with tap water. After rehydration, IR-ANF was elevated dramatically within 3 min and gradually for up to 1 h after water was offered; AVP decreased within 3 min of rehydration and stayed at the water-repleted level during the next 1 h. Na+, osm, and Hct did not change until 15, 9, and 30 min after rehydration, respectively. The rapid modifications in plasma IR-ANF and AVP were accompanied by a transient but significant increase in arterial blood pressure for up to 15 min after water consumption. These results indicate that oropharyngeal-gastric stimuli contribute to the release of both ANF and AVP.


1995 ◽  
Vol 269 (6) ◽  
pp. H1899-H1904 ◽  
Author(s):  
I. F. Pascoal ◽  
M. D. Lindheimer ◽  
C. Nalbantian-Brandt ◽  
J. G. Umans

We assessed KCl- and phenylephrine (PE)-induced vasoconstriction as well as acetylcholine (ACh)-induced endothelium-dependent vasodilation in small, isometrically mounted mesenteric arteries from virgin and gravid rats, studied in the absence and presence of NG-nitro-L-arginine (L-NNA). Neither maximal vasoconstriction nor PE potency differed significantly between vessels from virgin and pregnant rats, either in the absence or presence of L-NNA. L-NNA resulted in similar twofold leftward shifts in the PE dose-response curves for both groups. ACh-induced relaxation was potentiated in vessels from gravid rats (half-maximum effective concentration = 0.25 vs. 0.04 microM, virgin and gravid rats, respectively). After L-NNA, maximal relaxation was inhibited significantly more in vessels from gravid rats (62 vs. 31%). Likewise, maximal slope of ACh dose-response curves and ACh potency were decreased in this group so that values no longer differed from those in virgins. We conclude that pregnancy does not alter basal nitric oxide (NO) synthesis in these isolated microvessels, but it does enhance ACh-induced NO release, while apparently inhibiting the action of a NO-independent, endothelium-derived vasodilator.


1987 ◽  
Vol 252 (5) ◽  
pp. R921-R924 ◽  
Author(s):  
A. A. Khraibi ◽  
J. P. Granger ◽  
J. C. Burnett ◽  
K. R. Walker ◽  
F. G. Knox

The quantitative role of atrial natriuretic factor (ANF) in mediating the natriuresis induced by acute volume loading was determined in these studies. Plasma level of ANF (PANF), glomerular filtration rate (GFR), and renal excretory responses were measured in three groups of anesthetized Sprague-Dawley rats. In one group of rats (n = 8), acute volume expansion was established by intravenous infusion of saline (5% body wt) over a period of 30 min. A second group of rats (n = 13) was infused with synthetic ANF (2 micrograms X kg-1 X h-1 iv) to mimic the high PANF observed during acute volume loading. A third group (n = 13) served as control. PANF was similar and significantly elevated (P less than 0.05) in volume-expanded and ANF-infused groups compared with control. In control rats, PANF measured 122.0 +/- 12.1 pg/ml, whereas it averaged 389.4 +/- 30.3 pg/ml for volume-expanded and 368.1 +/- 22.3 pg/ml for ANF-infused rats. GFR was also comparable and significantly increased (P less than 0.05) in volume-expanded and ANF-infused groups compared with control rats. Infusion of ANF at a dose to mimic PANF obtained during acute volume expansion resulted in a fourfold increase in the fractional excretion of sodium. The results of these studies suggest that ANF may play an important quantitative role in promoting natriuresis during acute volume expansion.


1997 ◽  
Vol 272 (1) ◽  
pp. F87-F93
Author(s):  
S. Omer ◽  
P. Vaillancourt ◽  
K. G. Peri ◽  
D. R. Varma ◽  
S. Mulay

Using renal glomeruli and papillae from virgin, pregnant (15- to 17-day), and postpartum (day 2) rats, we investigated whether the decrease in the renal effects of atrial natriuretic factor (ANF) during pregnancy is caused by a downregulation of ANF receptors. Pregnancy decreased the maximal binding of 125I-labeled ANF to guanylyl cyclase (GC)-linked ANF-GC receptors in glomeruli and papillae and increased the binding to clearance receptors (ANF-C) in glomeruli; ANF-C receptors were not detected in the papillae Ribonuclease protection assay detected mRNAs for all the three receptors in the papillae; pregnancy decreased GC-A and ANF-C but not GC-B-receptor mRNAs. Western blots revealed a decrease in GC-A receptors in the papillae of pregnant rats; GC-B-receptor protein was barely detectable. Effects of ANF on guanosine 3', 5'-cyclic monophosphate (cGMP) production by the glomeruli and papillae were decreased during pregnancy and returned to virgin levels during postpartum. It is concluded that a decrease in the renal effects of ANF during pregnancy is caused by a downregulation of renal ANF GC-A receptors and receptor-coupled cGMP production.


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