Blood levels and renal effects of atrial natriuretic peptide in normal man.

Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important but not sole mechanism of natriuresis and diuresis induced by alpha hANP in man.

[1]  P. Weidmann,et al.  Cardiovascular counterregulation during sympathetic inhibition in normal subjects and patients with mild hypertension. , 1983, Hypertension.

[2]  P. Weidmann,et al.  Age versus urinary sodium for judging renin, aldosterone, and catecholamine levels: studies in normal subjects and patients with essential hypertension. , 1978, Kidney international.

[3]  J. Laragh,et al.  Atrial natriuretic factor inhibits angiotensin-, norepinephrine-, and potassium-induced vascular contractility. , 1984, Hypertension.

[4]  F. Murad,et al.  Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Kangawa,et al.  Purification and complete amino acid sequence of α-human atrial natriuretic polypeptide (α-hANP) , 1984 .

[6]  T. Goodfriend,et al.  Actions of synthetic atrial natriuretic factor on bovine adrenal glomerulosa. , 1984, Life sciences.

[7]  G. Düsterdieck,et al.  Estimation of Angiotensin II Concentration in Human Plasma by Radioimmunoassay. Some Applications to Physiological and Clinical States , 1971, European journal of clinical investigation.

[8]  P. Weidmann,et al.  Effects of human atrial natriuretic peptide on the pressor action of noradrenaline and angiotensin II in normal subjects. , 1985, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[9]  D. Giannessi,et al.  Radioimmunoassay of aldosterone in crude plasma extracts. , 1976, The Journal of nuclear biology and medicine.

[10]  A. J. Bold.  Heart atria granularity effects of changes in water-electrolyte balance. , 1979 .

[11]  D. Beasley,et al.  Atrial extracts increase glomerular filtration rate in vivo. , 1985, The American journal of physiology.

[12]  F. Smedes,et al.  Simple and fast solvent extraction system for selective and quantitative isolation of adrenaline, noradrenaline and dopamine from plasma and urine. , 1982, Journal of chromatography.

[13]  M. Cantin,et al.  Atrial natriuretic factor and urinary kallikrein in the rat: antagonistic factors? , 1984, Canadian journal of physiology and pharmacology.

[14]  Y. Hirata,et al.  Effects of atrial extract on blood pressure and urinary excretion of electrolytes and prostaglandin E2 in rats. , 1984, Prostaglandins, leukotrienes, and medicine.

[15]  J. Laragh,et al.  Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide , 1984, Nature.

[16]  D. Ganten,et al.  Vasopressin in brain of spontaneously hypertensive rats. , 1982, The American journal of physiology.

[17]  D. Jacobowitz,et al.  Evidence for the existence of atrial natriuretic factor-containing neurons in the rat brain. , 1985, Neuroendocrinology.

[18]  J. Granger,et al.  Effects of synthetic atrial natriuretic factor on renal function and renin release. , 1984, The American journal of physiology.

[19]  R. Keeler.  Atrial natriuretic factor has a direct, prostaglandin-independent action on kidneys. , 1982, Canadian journal of physiology and pharmacology.

[20]  R. Nutt,et al.  Specific membrane receptors for atrial natriuretic factor in renal and vascular tissues. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Webster,et al.  RENAL, HAEMODYNAMIC, AND HORMONAL EFFECTS OF HUMAN ALPHA ATRIAL NATRIURETIC PEPTIDE IN HEALTHY VOLUNTEERS , 1985, The Lancet.

[22]  S. Solomon,et al.  The effect of 6-hydroxydopamine on the renal responses to atrial natriuretic extract and blood volume expansion. , 1984, Proceedings of the Western Pharmacology Society.

[23]  J. P. Gilmore,et al.  Natriuretic Activity of Human and Monkey Atria , 1983, Circulation research.

[24]  M. Lie,et al.  Effect of glycine and glucagon on glomerular filtration and renal metabolic rates. , 1977, The American journal of physiology.

[25]  J. K. Chang,et al.  Depressor and natriuretic activities of several atrial peptides , 1984, Regulatory Peptides.

[26]  R. Gerzer,et al.  The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanylate cyclase , 1985, FEBS letters.

[27]  R. Nutt,et al.  Characterization of synthetic atrial natriuretic factor: vasodilator profile and decreased vascular sensitivity in hypertensive rats. , 1984, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[28]  J. Laragh,et al.  Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. , 1984, The American journal of physiology.

[29]  W. Cupples,et al.  The effect of a natriuretic atrial extract on renal haemodynamics and urinary excretion in anaesthetized rats. , 1983, The Journal of physiology.

[30]  U. Ackermann,et al.  Cardiovascular effects of atrial extracts in anesthetized rats. , 1984, Canadian journal of physiology and pharmacology.

[31]  M. Currie,et al.  Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria. , 1983, Science.

[32]  W. Cupples,et al.  Intrarenal localization of the natriuretic effect of cardiac atrial extract. , 1982 .

[33]  T. Flynn,et al.  The amino acid sequence of an atrial peptide with potent diuretic and natriuretic properties. , 1983, Biochemical and biophysical research communications.

[34]  H. Sonnenberg,et al.  Natriuretic effect of atrial extract on isolated perfused rat kidney. , 1983, Canadian journal of physiology and pharmacology.

[35]  K. Misono,et al.  Atrial natriuretic factor in rat hypothalamus, atria and plasma: determination by specific radioimmunoassay. , 1984, Biochemical and biophysical research communications.

[36]  H. Yoshimi,et al.  Specific receptors for atrial natriuretic factor (ANF) in cultured vascular smooth muscle cells of rat aorta. , 1984, Biochemical and biophysical research communications.

[37]  D. Ganten,et al.  Atrial natriuretic factor—a circulating hormone stimulated by volume loading , 1985, Nature.

[38]  S. G. Smith,et al.  Renal and systemic effects of synthetic atrial natriuretic factor. , 1985, Life sciences.

[39]  J. Rapp,et al.  Inhibition of aldosterone production by an atrial extract. , 1984, Science.

[40]  R. Keeler,et al.  Effects of atrial natriuretic factor on renal handling of water and electrolytes in rats. , 1983, Canadian journal of physiology and pharmacology.

[41]  M. Cantin,et al.  Atrial Natriuretic Factor: Characterization and Partial Purification , 1983, Hypertension.

[42]  D. Pollock,et al.  Effect of atrial extract on renal function in the rat. , 1983, Clinical science.

[43]  M. Ganguli,et al.  Dahl S rats have increased natriuretic factor in atria but are markedly hyporesponsive to it. , 1984, Hypertension.