Effects of endothelin (ET) on arterial pressure, fluid partition and plasma concentration of atrial natriuretic peptide (ANP): Influence of inhibition (I) of neutral endopeptidase (NEP) and phosphodiesterase (PDE) J.P. Valentin, C. Qiu, E. Wiedemann, D.G. Gardner, M.H. Humphreys. Divisions of Nephrology & Endocrinology, San Francisco General Hospital; Metabolic Research Unit, University of California San Francisco, San Francisco, CA, USA

Two natriuretic peptides, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), are found principally in the heart. In preliminary experiments with mouse kidney cells or slices, we found mouse BNP1-45 much more potent than ANP1-28 in causing elevations of cGMP (>50-fold). The guanylyl cyclase-A (GC-A) receptor has been suggested to represent the primary means by which both peptides signal. In cultured cells overexpressing GC-A, BNP and ANP were almost equivalent in potency, suggesting that a receptor unique for BNP exists in the kidney. However, in mice lacking the GC-A gene, neither BNP nor ANP significantly elevated cGMP in kidney slices. Phosphoramidon, a neutral endopeptidase inhibitor, shifted the apparent potency of ANP to values equivalent to that of BNP, suggesting these kidney cell/slices rapidly degrade ANP but not BNP. Mass spectroscopic analysis confirmed that ANP is rapidly cleaved at the first cysteine of the disulfide ring, whereas BNP is particularly stable to such cleavage. Other tissues (heart, aorta) failed to significantly degrade ANP or BNP, and therefore the kidney-specific degradation of ANP provides a mechanism for preferential regulation of kidney function by BNP independent of peripheral ANP concentration.Key words: guanylyl cyclase-A, atrial natriuretic peptide, B-type natriuretic peptide, neutral endopeptidase.

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Atrial natriuretic peptide increases resistance to venous return in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.252.5.h894 ◽

1987 ◽

Vol 252 (5) ◽

pp. H894-H899 ◽

Cited By ~ 4

Author(s):

Y. W. Chien ◽

E. D. Frohlich ◽

N. C. Trippodo

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Arterial Pressure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Total Peripheral Resistance ◽

Venous Return ◽

Venous Pressure ◽

Peripheral Resistance ◽

Atrial Natriuretic

To examine mechanisms by which administration of atrial natriuretic peptide (ANP) decreases venous return, we compared the hemodynamic effects of ANP (0.5 microgram X min-1 X kg-1), furosemide (FU, 10 micrograms X min-1 X kg-1), and hexamethonium (HEX, 0.5 mg X min-1 X kg-1) with those of vehicle (VE) in anesthetized rats. Compared with VE, ANP reduced mean arterial pressure (106 +/- 4 vs. 92 +/- 3 mmHg; P less than 0.05), central venous pressure (0.3 +/- 0.3 vs. -0.7 +/- 0.2 mmHg; P less than 0.01), and cardiac index (215 +/- 12 vs. 174 +/- 10 ml X min-1 X kg-1; P less than 0.05) and increased calculated resistance to venous return (32 +/- 3 vs. 42 +/- 2 mmHg X ml-1 X min X g; P less than 0.01). Mean circulatory filling pressure, distribution of blood flow between splanchnic organs and skeletal muscles, and total peripheral resistance remained unchanged. FU increased urine output similar to that of ANP, yet produced no hemodynamic changes, dissociating diuresis, and decreased cardiac output. HEX lowered arterial pressure through a reduction in total peripheral resistance without altering cardiac output or resistance to venous return. The results confirm previous findings that ANP decreases cardiac output through a reduction in venous return and suggest that this results partly from increased resistance to venous return and not from venodilation or redistribution of blood flow.

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Intrarenal atrial natriuretic peptide infusion lowers arterial pressure chronically

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.259.3.r585 ◽

1990 ◽

Vol 259 (3) ◽

pp. R585-R592 ◽

Cited By ~ 3

Author(s):

D. A. Hildebrandt ◽

H. L. Mizelle ◽

M. W. Brands ◽

C. A. Gaillard ◽

M. J. Smith ◽

...

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Atrial Natriuretic Peptide ◽

Renal Artery ◽

Natriuretic Peptide ◽

Recovery Period ◽

Arterial Plasma ◽

Chronically Instrumented Dogs ◽

Atrial Natriuretic

Chronic intravenous infusions of atrial natriuretic peptide (ANP) have been shown to lower mean arterial pressure (MAP) in both normal and hypertensive animals. However, the importance of the renal actions of ANP in mediating this hypotension is unknown. This study was designed to determine whether physiological or pathophysiological increases in intrarenal ANP levels influence long-term control of arterial pressure. ANP was infused into the renal artery of seven conscious, uninephrectomized, chronically instrumented dogs at 1, 2, and 4 ng.kg-1.min-1 for 7 days at each dose, followed by a recovery period. Then ANP was infused intravenously following the same protocol. MAP decreased from 88 +/- 3 to 78 +/- 3 mmHg during intrarenal infusion of 1 ng.kg-1.min-1 ANP; increasing the ANP infusion rate did not result in a further reduction in MAP. Systemic arterial plasma ANP concentration did not change from control (15 +/- 5 pg/ml) during 1 or 2 ng.kg-1.min-1 intrarenal ANP infusion but increased slightly during 4 ng.kg-1.min-1 intrarenal ANP infusion, averaging 53 +/- 11 pg/ml. Renal arterial plasma ANP concentrations were calculated to increase to approximately 120 +/- 5, 248 +/- 11, and 484 +/- 22 pg/ml during 1, 2, and 4 ng.kg-1.min-1 intrarenal ANP infusion, respectively. Intravenous ANP infusion did not alter MAP at 1 ng.kg-1.min-1, but MAP was slightly lower than control during 2 and 4 ng.kg-1.min-1 ANP infusion and remained below control during the postinfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

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