scholarly journals Differential effects of doxorubicin on atrial natriuretic peptide expression in vivo and in vitro

2001 ◽  
Vol 34 (3-4) ◽  
Author(s):  
ASIM RAHMAN ◽  
MAHMOOD ALAM ◽  
SUDHA RAO ◽  
LIN CAI ◽  
CLARK LUTHER T. ◽  
...  
1988 ◽  
Vol 74 (2) ◽  
pp. 207-211 ◽  
Author(s):  
A. Hughes ◽  
S. Thom ◽  
P. Goldberg ◽  
G. Martin ◽  
P. Sever

1. The effect of a α-human atrial natriuretic peptide (1–28) (ANP) on human vasculature was investigated in vivo and in vitro. Possible involvement of vascular dopamine receptors and the renin-angiotensin system in the response to ANP was also studied in vivo. 2. Forearm blood blow was measured by venous occlusion plethysmography. Isolated human blood vessels were studied using conventional organ bath techniques. 3. ANP (0.1–1 μg/min, intra-arterially) produced a dose-dependent increase in forearm blood flow, corresponding to a 163% increase in net forearm blood flow in the study arm. This action of ANP was not antagonized by (R)-sulpiride (100 μg/min, intra-arterially), a selective vascular dopamine receptor antagonist, or 50 mg of oral captopril, an inhibitor of angiotensin-converting enzyme. 4. ANP (1 nmol/l–1 μmol/l) produced concentration-dependent relaxation of isolated human arteries, including brachial artery, but was without effect on isolated human saphenous vein. 5. ANP produces vasodilatation in vivo and relaxes isolated human arterial smooth muscle. This action of ANP may contribute to its reported hypotensive effects in vivo.


1990 ◽  
Vol 258 (4) ◽  
pp. F998-F1004 ◽  
Author(s):  
H. M. Lafferty ◽  
M. Gunning ◽  
H. R. Brady ◽  
B. M. Brenner ◽  
S. Anderson

Manganese (Mn2+) is a cofactor for guanylate cyclase (GC), which is involved in the generation of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger for atrial natriuretic peptide (ANP) action. Mn2+ is also, however, a nonselective calcium-channel blocker. We examined the effects of infusion of MnCl2 into normal rats and its interaction in vivo and in vitro with GC and ANP. MnCl2 significantly increased glomerular filtration rate (GFR) and effective renal plasma flow rate (RPF). These effects were caused by selective afferent arteriolar vasodilatation, which allowed the glomerular capillary plasma flow rate and hydraulic pressure to rise, thus elevating single-nephron GFR. Urinary Na+ excretion (UNaV) also increased with MnCl2. The natriuresis was, unlike ANP, not mediated by GC activation and cGMP production, as MnCl2 had no effect on either urinary cGMP excretion or cGMP accumulation in intact inner medullary collecting duct cell (IMCD) suspensions, nor did it affect Na(+)-dependent oxygen consumption in these cells. When superimposed on an infusion of ANP, MnCl2 resulted in significant increases in UNaV, GFR, and RPF. These effects were associated with small but significant increments in urinary cGMP excretion. However, MnCl2 did not affect in vitro cGMP production in intact IMCDs or glomeruli in response to ANP stimulation. It is uncertain therefore whether the in vivo augmentation of the natriuretic effect of ANP by MnCl2 is related to GC activation and cGMP production.


1989 ◽  
Vol 120 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Mitsuaki Nakamaru ◽  
Toshio Ogihara ◽  
Hiroshi Saito ◽  
Hiromi Rakugi ◽  
Kiyoko Hashizume ◽  
...  

Abstract. The effect of synthetic alpha human atrial natriuretic peptide on catecholamine release from human pheochromocytomas was studied both in vivo and in vitro. Iv infusion of atrial natriuretic peptide at a rate of 0.1 μg ·kg−1·min−1 for 60 min into two normotensive patients with pheochromocytoma caused a small decrease in the mean blood pressure, increase in the heart rate, and marked increase in the plasma level of norepinephrine (2.08 to 6.83 nmol/l, and 1.15 to 2.83 nmol/l, respectively) compared with 0.60 ± 0.10 to 1.19 ± 0.20 nmol/l in normal subjects. Treatment with atrial natriuretic peptide also increased the plasma epinephrine level from 0.34 to 1.27 nmol/l, and from 0.67 to 0.79 nmol/l in the patients with pheochromocytoma, but not in the normal subjects (0.05 ± 0.01 to 0.05 ± 0.01 nmol/l). After removal of the tumour, the responses of the plasma norepinephrine and epinephrine to atrial natriuretic peptide infusion were normalized. There was no significant effect of 10−8 to 10−5 mol/l atrial natriuretic peptide on the basal release of catecholamines from isolated superfused pheochromocytoma tissue. Atrial natriuretic peptide (10−7 mol/l) did not affect the increase in catecholamine release induced by glucagon (10−5 mol/l). These results suggest that the exaggerated responses of plasma catecholamines to atrial natriuretic peptide in patients with pheochromocytoma may be due to a washout effect resulting from change in blood flow in the vessels feeding the tumour rather than increased sympathetic nerve activity induced by hypotension and hypovolemia. The results also suggest that atrial natriuretic peptide dose not have any direct action on pheochromocytoma tissue causing catecholamine release.


1987 ◽  
Vol 115 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Sadao Nakajima ◽  
Hiromichi Suzuki ◽  
Ikuo Saito ◽  
Takao Saruta

Abstract. This study was undertaken to examine the effects of atrial natriuretic peptide (ANP), dopamine, and ouabain, which each are considered to be a kind of natriuretic factor, on aldosterone synthesis in vivo and in vitro. In the in vivo experiments, during infusion of one of the natriuretic factors, ANP (64 pmol · min−1 · kg−1), dopamine (20 nmol · min−1 · kg−1) or ouabain (684 pmol · min−1 · kg−1), the stimulatory action of angiotensin II (20 pmol · min−1 · kg−1) or adrenocorticotropin (ACTH, 7 pmol · min−1 · kg−1) on aldosterone synthesis was investigated in 36 anaesthetized (pentobarbital, 40 mg/kg, iv) female rabbits. In the basal condition, aldosterone synthesis was suppressed slightly by each of the natriuretic factors. The stimulatory actions of angiotensin II and ACTH on aldosterone synthesis were significantly attenuated by pre-treatment with ANP and dopamine. However, ouabain infusion did not induce any changes in the synthesis of aldosterone, 18-hydroxycorticosterone (18-OHB), and corticosterone (B) in either the basal or the stimulated conditions. For the in vitro experiments, rabbit adrenal glomerulosa cells (105 cells/tube) were used. The effects of ANP and dopamine on the aldosterone synthesis revealed results identical to those from the in vivo study. However, in contrast to the in vivo study, ouabain completely inhibited the synthesis of aldosterone, 18-OHB and B. The above results obtained in vivo and in vitro suggest that ANP inhibits corticosterone methyloxidase II activity and dopamine inhibits corticosterone methyloxidase I activity. However, from the present study we were unable to specify the action of ouabain on the synthesis of aldosterone and its related substances.


1992 ◽  
Vol 19 (10) ◽  
pp. 711-716 ◽  
Author(s):  
Toshihiko Ishimitsu ◽  
Yasunobu Hirata ◽  
Hiroaki Matsuoka ◽  
Masao Ishii ◽  
Tsuneaki Sugimoto ◽  
...  

Biomaterials ◽  
2008 ◽  
Vol 29 (36) ◽  
pp. 4783-4791 ◽  
Author(s):  
Danielle N. Rockwood ◽  
Robert E. Akins ◽  
Ian C. Parrag ◽  
Kimberly A. Woodhouse ◽  
John F. Rabolt

1986 ◽  
Vol 8 (6) ◽  
pp. 1323 ◽  
Author(s):  
J. C. Burnett ◽  
G. M. Rubanyi ◽  
B. S. Edwards ◽  
T. R. Schwab ◽  
R. S. Zimmerman ◽  
...  

1994 ◽  
Vol 4 (12) ◽  
pp. 2016-2022
Author(s):  
J L Logan ◽  
U F Michael

Atrial natriuretic peptide (ANP) inhibits the growth of a variety of cell types in vitro including mesangial cells. The effects of ANP on the growth of the kidney in vivo were evaluated. A 2-h infusion of 0.2 microgram/250 g body wt per minute of ANP suppressed the subsequent uptake of [3H]thymidine into the renal DNA of uninephrectomized but not intact rats. This treatment also depressed the ratio of RNA/DNA in kidneys undergoing compensatory growth. Correlative physiologic studies revealed enhanced GFR in rats with two kidneys infused with ANP, but no increase in the GFR of uninephrectomized rats. It was concluded that ANP may oppose the growth factor(s) mediating compensatory renal growth.


1994 ◽  
Vol 77 (3) ◽  
pp. 1309-1316 ◽  
Author(s):  
J. R. Klinger ◽  
F. Arnal ◽  
R. R. Warburton ◽  
L. C. Ou ◽  
N. S. Hill

We hypothesized that a downregulation in pulmonary atrial natriuretic peptide (ANP) receptors helps raise plasma ANP levels during chronic hypoxia. We measured in vivo pulmonary uptake and plasma clearance of 125I-ANP and in vitro pulmonary binding kinetics of 125I-ANP in normoxic and chronically hypoxic rats. Exposure to 21 days of hypobaric (0.5 atm) hypoxia did not decrease specific binding of 125I-ANP in the kidney, but pulmonary binding decreased 35 and 75% after 1 and 3 days of hypoxia, respectively, and increased 200% after 3 days of normoxic recovery from 21 days of hypoxia. The total binding capacity for ANP to lung membrane fractions from normoxic rats, chronically hypoxic rats, and rats that had recovered from hypoxia was 488 +/- 59, 109 +/- 17, and 338 +/- 48 fmol/mg, respectively (P < 0.05 for hypoxic vs. normoxic or recovered lung membranes). The area under the 125I-ANP plasma concentration curve for normoxic and hypoxic rats and normoxic rats that were infused with the ANP C-receptor ligand C-ANF-(4–23) was 3,292 +/- 216, 5,022 +/- 466, and 8,205 +/- 1,059 disintegrations.min-1.ml–1, respectively [P < 0.05 for hypoxic vs. normoxic or C-ANF-(4–23)-infused rats]. We conclude that pulmonary ANP clearance is reduced during chronic hypoxia secondary to a downregulation in pulmonary ANP clearance receptors. Reduced pulmonary clearance of ANP may represent an adaptation that contributes to increased plasma ANP levels during chronic hypoxia.


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