AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 2
April 1990
RELATIONSHIP BETWEEN PLASMA RENIN CONCENTRATION AND ATRIAL NATRIURETIC PEPTIDE IN THE HUMAN NEWBORN Jaime Tannenbaum, M.D., Sonia Hulman, M.D., and Bonita Falkner, M.D.
To test the hypothesis that atrial natriuretic peptide (ANP) concentration in the newborn is negatively related to plasma renin concentration (PRC), as it is in the adult, we measured the concentration of both substances in the same plasma sample. We studied 24 well term newborns and 20 samples of umbilical venous blood from normal deliveries. Both ANP and PRC are elevated in newborn plasma, but not in umbilical venous plasma. ANP levels on the second day of life are greater than either day 1 or day 3. Linear regression of ANP and PRC demonstrates a highly significant negative correlation [r = —0.65, p < 0.001], which suggests that the suppression of the renin-angiotensin system by ANP seen in the adult may be intact in the newborn. ANP may act to blunt the effects of the augmented renin-angiotensin system of the newborn and promote normal neonatal diuresis.
Atrial natriuretic peptide (ANP) is a recently characterized cardiac hormone, which contributes to the physiologic regulation of intravascular volume. Recent literature indicates that ANP may also be an important factor in the regulation of intravascular volume and blood pressure in the newborn. ANP may act in concert with the classically described renin-angiotensin pathway. Experimental1 and clinical2 investigations have demonstrated an inverse correlation between ANP and plasma renin activity (PRA) in normal adults. These reports have shown that the prevailing hemodynamic status determines the dominance of one hormone over the other. This project was designed to investigate the interrelationship of ANP and plasma renin concentration (PRC) in the normal neonate. We hypothesize that the negative correlation between ANP and PRC as reported in adults is also preserved in the human newborn. This relationship may be a controlling element in the regulation of intravascular volume and blood pressure during the hemodynamic transition from fetal to neonatal life.
METHODS
Newborn infants delivered at term without obstetrical or neonatal complications were enrolled in this study. Written informed consent was obtained from mothers of all subjects prior to enrollment under the guidelines of the Hahnemann University Institutional Review Board. Umbilical cord blood samples were obtained at delivery from healthy term infants. Percutaneous venous samples of blood were obtained from healthy newborns within the first 78 hours of life. The age of the infant in hours was recorded for each sample. Samples were drawn into chilled tubes containing ethylene diaminetetra acetic acid and were centrifuged within 15 minutes of collection. The plasma was stored at — 80°C until analysis. Samples were assayed for ANP (n = 24) by radioimmunoassay (Peninsula) on 0.5 ml of plasma following an extraction procedure. PRC and plasma renin substrate (PRS) (n = 14) were measured on plasma by radioimmunoassay by the method of Gould et al.3 PRA could not be accurately measured
Department of Pediatrics, Hahnemann University, Philadelphia, Pennsylvania Reprint requests: Dr. Hulman, Department of Pediatrics, Hahnemann University, Broad and Vine Streets, Philadelphia, PA 19102
174
Copyright © 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: NYU. Copyrighted material.
ABSTRACT
PLASMA RENIN AND ATRIAL NATRIURETIC PEPTIDE/Tannenbaum, Hulman, Falkner Plasma Renin Concentration vs ANP Concentration
on such small plasma volumes. However, the volume of plasma has no effect on the computed result of PRC. Therefore the relationship between ANP and PRC was examined. Standard neonatal data obtained on each infant included birthweight, daily weight, and Apgar scores. The gestational age was assessed by maternal menstrual history and confirmed by physical examination using the method of Dubowitz et al.4 y . -0.29x + 146.2 r« -0.65 p< 0.001
The study population consisted of 24 neonates, age 10 hours to 78 hours and 20 umbilical cord samples. Birthweight, gestational age and Apgar scores of the infants showed no differences in these measures between 7 infants delivered by cesarean versus 17 by standard vaginal delivery. There was no detectable difference in plasma levels of ANP, PRC, or PRS between infants born by either method of delivery. Table 1 contains the mean concentrations of ANP, PRC, and PRS in infants and cord blood. Also included in the table are the values for normal adults from this laboratory. The mean ANP concentration is significantly greater in the newborn than in cord blood (p < 0.001). ANP was also significantly greater in the newborn than in adult normal subjects (p < 0.001). PRC and PRS are also higher in the newborn when compared with cord blood and adult control subjects. The ANP data were analyzed as a function of postdelivery age in hours. ANP levels increased to 169 ± 97 pg/ml in the first 24 hours (n = 5); to 245 ± 109 pg/ml at 24 to 48 hours (n = 6); and then fell to 163 ± 91 pg/ml by 72 hours (n = 13). In Figure 1, plasma ANP concentration is presented as a function of PRC. A statistically significant negative linear correlation exists between ANP concentration and PRC r = -0.65, p < 0.001). There is no statistical relationship between ANP and PRS. DISCUSSION
This study demonstrates that both ANP and PRC are elevated in the newborn period. Despite the marked elevations of both substances, there is a significant inverse relationship between plasma ANP concentration and PRC in the immediate postnatal period.
Table 1.
Figure 1 . The values for plasma renin concentration (PRC) and atrial natriuretic peptide aredepicted for each subject. Regression analysis demonstrates a significant negative correlation (p < 0.001).
ANP is a 28 amino acid polypeptide that is synthesized and stored in atrial myocytes. Conditions that induce mechanical stretch of the atria, such as an increase in intravascular volume, stimulate degranulation and release of ANP. 56 The changing hemodynamics at birth, including closure of the ductus arteriosus, requires the right heart to pump against an increased pulmonary vascular resistance; the left ventricle must also pump against a gradually increasing systemic vascular resistance. These hemodynamic shifts may result in increased atrial pressure and stretch. Animal and human studies have reported elevated levels of ANP in fetal plasma. Cheung et al7 demonstrated fetal ANP levels 5.6 times greater than maternal ANP levels with no difference in ANP concentration between umbilical arterial and venous plasma. Yamaji et al,8 however, demonstrated that the mean umbilical cord arterial plasma ANP concentration was significantly higher than that in cord venous plasma. In addition, Robillard et al9 have shown that the human fetus is able to release ANP in response to an increase in atrial volume and/or pressure. Our data from umbilical cord plasma indicate that ANP is present in very low quantities at the time of delivery. Thus, it is unclear what role ANP may play in the regulation of the hemodynamic status of the fetus. ANP has been shown to induce a marked diuresis, natriuresis, and kaliuresis,10"12 a slight but significant decrease in blood pressure,13 a decrease in
ANP, PRC, and PRS in Study Group
Mean ± SD
Cord (n = 20)
Normal Baby (n = 24)
Adult*
ANP (pg/ml)
2.27 ± 4.2 46.9 ± 27.6 1049 ± 349
187.0 ± 94.4 83.4 ± 47.1 1531 ± 403
29.9 ± 15.9 41.0 ± 6.0 761 ± 31.0
PRC+ (|JLU)
PRS+ (pmol/ml)
*Normal adult values for laboratory of Could et al.3 Measured on 14 cases.
+
Downloaded by: NYU. Copyrighted material.
RESULTS
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AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 2
176
animal studies. 1423 The inhibitory effect on renin release is most apparent when the basal secretion rate of renin is elevated.22 This is consistent with our data, which suggest that not only does the neonate exhibit significantly greater values of PRC, but also that renin concentration is inversely proportional to ANP concentration. ANP infusion in normotensive dogs results in a significant and reversible decrease in plasma aldosterone concentration.1 The reduction in aldosterone may be due, in part, to ANPs inhibition of renin secretion. However, it has also been reported that ANP directly inhibits the production of aldosterone at the level of the zona glomerulosa 1113 by inhibiting the conversion of cholesterol to progesterone.16 With aldosterone suppression, distal tubule reabsorption of sodium and water is impaired, perhaps augmenting the diuretic effect of ANP. CONCLUSION
The postnatal surge of ANP demonstrated in this study may explain the postnatal diuresis seen in the human newborn. In addition, the inverse relationship between ANP and PRA in the newborn is similar to that of the adult. This reinforces the possibility that ANP may act in opposition to the RAAS in the human newborn. REFERENCES
1. Maack T, Marion D, Camargo MJ, Kleinhart HD, Lavagh JH, Vaughan ED, Atlas SA: Effects of auriculum (ANF) on blood pressure, renal function, and renin-aldosterone system in dogs. Am J Med 77:1069-1075, 1984 2. Shenker Y, Sider RS, Ostefin EA, Grekin RJ: Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema. J Clin Invest 76:1684— 1687, 1985 3. Gould AB, Goodman S, DeWolf R, Onesti G, Swartz C: Measurement of renin and substrate concentrations in human serum. Ann BioChem 94:125-139, 1979 4. Dubowitz L, Dubowitz V, Goldberg C: Clinical assessment of gestational age in the newborn infant. J Pediatr 77:1-10, 1970 5. Jamieson JD, Palade GE: Specific granules in atrial muscle cells. J Cell Biol 23:151-172, 1964 6. Sonnenberg H: Mechanisms of release and renal tubular action of atrial natriuretic factor. Fed Proc 45:21062110, 1986 7. Cheung CY, Gibbs DM, Brace RA: Atrial natriuretic factor in maternal and fetal sheep. Am J Physiol 252(2Ptl): E279-282, 1987 8. Yamaji T, Hirai N, Ishibashi M, Takaku F, Yanaihara T: Atrial natriuretic peptide in umbilical cord blood: Evidence for a circulating hormone in human fetus. J Clin Endocrinol Metab 63:1414-1417, 1986 9. Robillard JE, Weiner CP: Effect of volume expansion on atrial natriuretic factor (ANF) in the human fetus. Pediatr Res 23:423A, 1988 10. DeBold AJ, Borenstein HB, Veress AT, Sonnenberg H: A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats. Life Sci 28: 89-94, 1981 11. Atlas SA: Atrial natriuretic factor: Renal and systemic effects. Hosp Prac 21:67-77, 1986
Downloaded by: NYU. Copyrighted material.
the release of renin, 1314 and an inhibition of aldosterone secretion by the adrenal zona glomerulosa cells.13-15-16 There are several proposed mechanisms by which ANP may induce a diuresis and natriuresis. ANP induces an increase in the glomerular nitration rate, 1 2 1 3 resulting in an increased load of sodium and chloride delivered to the distal tubule. Maack et al12 have reported that ANP may modify the intrarenal distribution of blood flow, causing an increase in medullary and papillary flow with subsequent medullary washout and disruption of the medullary concentration gradient. In addition, ANP selectively contracts the efferent arteriole and relaxes the afferent arteriole,11 leading to an increase in the intraglomerular hydrostatic pressure. Finally, in conscious dogs, infusion of ANP produced a prolonged redistribution of blood flow to the middle and outer cortexes, the region containing the more salt-losing nephrons. Thus, in the newborn, ANP may effect a shift in the regional blood flow of the kidney. Previous reports indicate that the neonate has increased renal vascular resistance, decreased renal bloodflow,and decreased glomerular filtration rate when compared with normal adult.17"19 Kotchen et al20 reported that the newborn has an augmented renin-angiotensin-aldosterone system (RAAS) when compared with adult normal persons. In spite of this antidiuretic environment, the newborn undergoes a diuresis of up to 10% of its total body weight within the first few days of life.21 The surge of ANP within the first 40 to 50 hours of life described in this report may contribute to this postnatal diuresis seen in the newborn. Blood pressure levels in the normal neonate are lower compared with normotensive children and adults. The high plasma levels of ANP in the neonate may oppose the pressor effects of an augmented RAAS. The effect of ANP on blood pressure regulation may be due in part to its ability to cause relaxation of vascular smooth muscle. It has been demonstrated that, in order for ANP to induce relaxation of vascular smooth muscle, the vessel must first be constricted by hormonal or nonhormonal agonists.13 The high circulating levels of angiotensin II in the neonate may establish the proper environment for ANP to induce vasodilation and decrease the peripheral vascular resistance. Volpe et al 22 have demonstrated that ANPs ability to lower blood pressure is enhanced in a renin dependent hypertensive model in which high levels of circulating renin exist. In their study, infusion of synthetic ANP into Goldblatt hypertensive rats induced a more profound reduction in blood pressure when the concentrations of circulating renin and angiotensin II were elevated. The elevated levels of plasma renin activity in the newborn have been well documented.20 Consequently, an environment exists for the enhanced physiologic effect of ANP, with resultant lower blood pressure. Constant infusion of ANP has been shown to lead to a marked inhibition of renin secretion in
April 1990
PLASMA RENIN A N D ATRIAL NATRIURETIC PEPTIDE/Tannenbaum, Hulman, Falkner
19. 20. 21. 22.
23.
lar filtration rate in the first three weeks of life. J Pediatr 87:268-272, 1975 Fawer CL, Torrado A, Guignard JP: Maturation of renal function in full term and premature neonates. Helv Paediatr Acta 34:11-21, 1979 Kotchen TA, Strickland AL, Rice TW, Walters DR: A study of the renin-angiotensin system in newborn infants. J Pediatr 80:938-946, 1972 Phibbs RH: The newborn infant. In Rudolph AM (ed): Pediatrics. Norwalk, CT: Appleton-Century-Crofts, 1982, pp 130-131 Volpe M, Odell G, Kleinert HD, Miller F, Camargo MJ, Laragh JH, Maack T, Vaughan ED, Atlas SA: Effect of atrial natriuretic factor on blood pressure, renin, and aldosterone in Goldblatt hypertension. Hypertension 7 (Suppl I):I43-I48, 1985 Laragh JH: Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure-electrolyte homeostasis. N Engl J Med 313:1330-1340, 1985
Downloaded by: NYU. Copyrighted material.
12. Maack T, Atlas SA, Camargo MJF, Cogan MG: Renal hemodynamic and natriuretic effects of atrial natriuretic factor. Fed Proc 45:2128-2132, 1985 13. Atlas SA, Volpe M, Sosa RE, Laragh JH, Camargo MJF: Effects of atrial natriuretic factor on blood pressure and the renin-angiotensin-aldosterone system. Fed Proc 45: 2115-2121, 1986 14. Antonipillai L, Vogelsang J, Horton R: Role of atrial natriuretic factor in renin release. Endocrinology 119:318322, 1986 15. Vari RC, Freeman RH, Davis JO, Villarreal D, Verburg KM: Effect of synthethic atrial natriuretic factor on aldosterone secretion in the rat. Am J Physiol 251(lPt2):R4852, 1986 16. Elliott ME, Goodfriend TL: Inhibition of aldosterone synthesis by atrial natriuretic factor. Fed Proc 45:2376— 2381, 1986 17. Kleinman LI: Developmental renal physiology. Physiologist 25:104-110, 1981 18. Guignard JP, Torrado A, DaCunha O, Gautier E: Glomeru-
177
April 1990
RELATIONSHIP BETWEEN PLASMA RENIN CONCENTRATION AND ATRIAL NATRIURETIC PEPTIDE IN THE HUMAN NEWBORN Jaime Tannenbaum, M.D., Sonia Hulman, M.D., and Bonita Falkner, M.D.
To test the hypothesis that atrial natriuretic peptide (ANP) concentration in the newborn is negatively related to plasma renin concentration (PRC), as it is in the adult, we measured the concentration of both substances in the same plasma sample. We studied 24 well term newborns and 20 samples of umbilical venous blood from normal deliveries. Both ANP and PRC are elevated in newborn plasma, but not in umbilical venous plasma. ANP levels on the second day of life are greater than either day 1 or day 3. Linear regression of ANP and PRC demonstrates a highly significant negative correlation [r = —0.65, p < 0.001], which suggests that the suppression of the renin-angiotensin system by ANP seen in the adult may be intact in the newborn. ANP may act to blunt the effects of the augmented renin-angiotensin system of the newborn and promote normal neonatal diuresis.
Atrial natriuretic peptide (ANP) is a recently characterized cardiac hormone, which contributes to the physiologic regulation of intravascular volume. Recent literature indicates that ANP may also be an important factor in the regulation of intravascular volume and blood pressure in the newborn. ANP may act in concert with the classically described renin-angiotensin pathway. Experimental1 and clinical2 investigations have demonstrated an inverse correlation between ANP and plasma renin activity (PRA) in normal adults. These reports have shown that the prevailing hemodynamic status determines the dominance of one hormone over the other. This project was designed to investigate the interrelationship of ANP and plasma renin concentration (PRC) in the normal neonate. We hypothesize that the negative correlation between ANP and PRC as reported in adults is also preserved in the human newborn. This relationship may be a controlling element in the regulation of intravascular volume and blood pressure during the hemodynamic transition from fetal to neonatal life.
METHODS
Newborn infants delivered at term without obstetrical or neonatal complications were enrolled in this study. Written informed consent was obtained from mothers of all subjects prior to enrollment under the guidelines of the Hahnemann University Institutional Review Board. Umbilical cord blood samples were obtained at delivery from healthy term infants. Percutaneous venous samples of blood were obtained from healthy newborns within the first 78 hours of life. The age of the infant in hours was recorded for each sample. Samples were drawn into chilled tubes containing ethylene diaminetetra acetic acid and were centrifuged within 15 minutes of collection. The plasma was stored at — 80°C until analysis. Samples were assayed for ANP (n = 24) by radioimmunoassay (Peninsula) on 0.5 ml of plasma following an extraction procedure. PRC and plasma renin substrate (PRS) (n = 14) were measured on plasma by radioimmunoassay by the method of Gould et al.3 PRA could not be accurately measured
Department of Pediatrics, Hahnemann University, Philadelphia, Pennsylvania Reprint requests: Dr. Hulman, Department of Pediatrics, Hahnemann University, Broad and Vine Streets, Philadelphia, PA 19102
174
Copyright © 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
Downloaded by: NYU. Copyrighted material.
ABSTRACT
PLASMA RENIN AND ATRIAL NATRIURETIC PEPTIDE/Tannenbaum, Hulman, Falkner Plasma Renin Concentration vs ANP Concentration
on such small plasma volumes. However, the volume of plasma has no effect on the computed result of PRC. Therefore the relationship between ANP and PRC was examined. Standard neonatal data obtained on each infant included birthweight, daily weight, and Apgar scores. The gestational age was assessed by maternal menstrual history and confirmed by physical examination using the method of Dubowitz et al.4 y . -0.29x + 146.2 r« -0.65 p< 0.001
The study population consisted of 24 neonates, age 10 hours to 78 hours and 20 umbilical cord samples. Birthweight, gestational age and Apgar scores of the infants showed no differences in these measures between 7 infants delivered by cesarean versus 17 by standard vaginal delivery. There was no detectable difference in plasma levels of ANP, PRC, or PRS between infants born by either method of delivery. Table 1 contains the mean concentrations of ANP, PRC, and PRS in infants and cord blood. Also included in the table are the values for normal adults from this laboratory. The mean ANP concentration is significantly greater in the newborn than in cord blood (p < 0.001). ANP was also significantly greater in the newborn than in adult normal subjects (p < 0.001). PRC and PRS are also higher in the newborn when compared with cord blood and adult control subjects. The ANP data were analyzed as a function of postdelivery age in hours. ANP levels increased to 169 ± 97 pg/ml in the first 24 hours (n = 5); to 245 ± 109 pg/ml at 24 to 48 hours (n = 6); and then fell to 163 ± 91 pg/ml by 72 hours (n = 13). In Figure 1, plasma ANP concentration is presented as a function of PRC. A statistically significant negative linear correlation exists between ANP concentration and PRC r = -0.65, p < 0.001). There is no statistical relationship between ANP and PRS. DISCUSSION
This study demonstrates that both ANP and PRC are elevated in the newborn period. Despite the marked elevations of both substances, there is a significant inverse relationship between plasma ANP concentration and PRC in the immediate postnatal period.
Table 1.
Figure 1 . The values for plasma renin concentration (PRC) and atrial natriuretic peptide aredepicted for each subject. Regression analysis demonstrates a significant negative correlation (p < 0.001).
ANP is a 28 amino acid polypeptide that is synthesized and stored in atrial myocytes. Conditions that induce mechanical stretch of the atria, such as an increase in intravascular volume, stimulate degranulation and release of ANP. 56 The changing hemodynamics at birth, including closure of the ductus arteriosus, requires the right heart to pump against an increased pulmonary vascular resistance; the left ventricle must also pump against a gradually increasing systemic vascular resistance. These hemodynamic shifts may result in increased atrial pressure and stretch. Animal and human studies have reported elevated levels of ANP in fetal plasma. Cheung et al7 demonstrated fetal ANP levels 5.6 times greater than maternal ANP levels with no difference in ANP concentration between umbilical arterial and venous plasma. Yamaji et al,8 however, demonstrated that the mean umbilical cord arterial plasma ANP concentration was significantly higher than that in cord venous plasma. In addition, Robillard et al9 have shown that the human fetus is able to release ANP in response to an increase in atrial volume and/or pressure. Our data from umbilical cord plasma indicate that ANP is present in very low quantities at the time of delivery. Thus, it is unclear what role ANP may play in the regulation of the hemodynamic status of the fetus. ANP has been shown to induce a marked diuresis, natriuresis, and kaliuresis,10"12 a slight but significant decrease in blood pressure,13 a decrease in
ANP, PRC, and PRS in Study Group
Mean ± SD
Cord (n = 20)
Normal Baby (n = 24)
Adult*
ANP (pg/ml)
2.27 ± 4.2 46.9 ± 27.6 1049 ± 349
187.0 ± 94.4 83.4 ± 47.1 1531 ± 403
29.9 ± 15.9 41.0 ± 6.0 761 ± 31.0
PRC+ (|JLU)
PRS+ (pmol/ml)
*Normal adult values for laboratory of Could et al.3 Measured on 14 cases.
+
Downloaded by: NYU. Copyrighted material.
RESULTS
175
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 2
176
animal studies. 1423 The inhibitory effect on renin release is most apparent when the basal secretion rate of renin is elevated.22 This is consistent with our data, which suggest that not only does the neonate exhibit significantly greater values of PRC, but also that renin concentration is inversely proportional to ANP concentration. ANP infusion in normotensive dogs results in a significant and reversible decrease in plasma aldosterone concentration.1 The reduction in aldosterone may be due, in part, to ANPs inhibition of renin secretion. However, it has also been reported that ANP directly inhibits the production of aldosterone at the level of the zona glomerulosa 1113 by inhibiting the conversion of cholesterol to progesterone.16 With aldosterone suppression, distal tubule reabsorption of sodium and water is impaired, perhaps augmenting the diuretic effect of ANP. CONCLUSION
The postnatal surge of ANP demonstrated in this study may explain the postnatal diuresis seen in the human newborn. In addition, the inverse relationship between ANP and PRA in the newborn is similar to that of the adult. This reinforces the possibility that ANP may act in opposition to the RAAS in the human newborn. REFERENCES
1. Maack T, Marion D, Camargo MJ, Kleinhart HD, Lavagh JH, Vaughan ED, Atlas SA: Effects of auriculum (ANF) on blood pressure, renal function, and renin-aldosterone system in dogs. Am J Med 77:1069-1075, 1984 2. Shenker Y, Sider RS, Ostefin EA, Grekin RJ: Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema. J Clin Invest 76:1684— 1687, 1985 3. Gould AB, Goodman S, DeWolf R, Onesti G, Swartz C: Measurement of renin and substrate concentrations in human serum. Ann BioChem 94:125-139, 1979 4. Dubowitz L, Dubowitz V, Goldberg C: Clinical assessment of gestational age in the newborn infant. J Pediatr 77:1-10, 1970 5. Jamieson JD, Palade GE: Specific granules in atrial muscle cells. J Cell Biol 23:151-172, 1964 6. Sonnenberg H: Mechanisms of release and renal tubular action of atrial natriuretic factor. Fed Proc 45:21062110, 1986 7. Cheung CY, Gibbs DM, Brace RA: Atrial natriuretic factor in maternal and fetal sheep. Am J Physiol 252(2Ptl): E279-282, 1987 8. Yamaji T, Hirai N, Ishibashi M, Takaku F, Yanaihara T: Atrial natriuretic peptide in umbilical cord blood: Evidence for a circulating hormone in human fetus. J Clin Endocrinol Metab 63:1414-1417, 1986 9. Robillard JE, Weiner CP: Effect of volume expansion on atrial natriuretic factor (ANF) in the human fetus. Pediatr Res 23:423A, 1988 10. DeBold AJ, Borenstein HB, Veress AT, Sonnenberg H: A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats. Life Sci 28: 89-94, 1981 11. Atlas SA: Atrial natriuretic factor: Renal and systemic effects. Hosp Prac 21:67-77, 1986
Downloaded by: NYU. Copyrighted material.
the release of renin, 1314 and an inhibition of aldosterone secretion by the adrenal zona glomerulosa cells.13-15-16 There are several proposed mechanisms by which ANP may induce a diuresis and natriuresis. ANP induces an increase in the glomerular nitration rate, 1 2 1 3 resulting in an increased load of sodium and chloride delivered to the distal tubule. Maack et al12 have reported that ANP may modify the intrarenal distribution of blood flow, causing an increase in medullary and papillary flow with subsequent medullary washout and disruption of the medullary concentration gradient. In addition, ANP selectively contracts the efferent arteriole and relaxes the afferent arteriole,11 leading to an increase in the intraglomerular hydrostatic pressure. Finally, in conscious dogs, infusion of ANP produced a prolonged redistribution of blood flow to the middle and outer cortexes, the region containing the more salt-losing nephrons. Thus, in the newborn, ANP may effect a shift in the regional blood flow of the kidney. Previous reports indicate that the neonate has increased renal vascular resistance, decreased renal bloodflow,and decreased glomerular filtration rate when compared with normal adult.17"19 Kotchen et al20 reported that the newborn has an augmented renin-angiotensin-aldosterone system (RAAS) when compared with adult normal persons. In spite of this antidiuretic environment, the newborn undergoes a diuresis of up to 10% of its total body weight within the first few days of life.21 The surge of ANP within the first 40 to 50 hours of life described in this report may contribute to this postnatal diuresis seen in the newborn. Blood pressure levels in the normal neonate are lower compared with normotensive children and adults. The high plasma levels of ANP in the neonate may oppose the pressor effects of an augmented RAAS. The effect of ANP on blood pressure regulation may be due in part to its ability to cause relaxation of vascular smooth muscle. It has been demonstrated that, in order for ANP to induce relaxation of vascular smooth muscle, the vessel must first be constricted by hormonal or nonhormonal agonists.13 The high circulating levels of angiotensin II in the neonate may establish the proper environment for ANP to induce vasodilation and decrease the peripheral vascular resistance. Volpe et al 22 have demonstrated that ANPs ability to lower blood pressure is enhanced in a renin dependent hypertensive model in which high levels of circulating renin exist. In their study, infusion of synthetic ANP into Goldblatt hypertensive rats induced a more profound reduction in blood pressure when the concentrations of circulating renin and angiotensin II were elevated. The elevated levels of plasma renin activity in the newborn have been well documented.20 Consequently, an environment exists for the enhanced physiologic effect of ANP, with resultant lower blood pressure. Constant infusion of ANP has been shown to lead to a marked inhibition of renin secretion in
April 1990
PLASMA RENIN A N D ATRIAL NATRIURETIC PEPTIDE/Tannenbaum, Hulman, Falkner
19. 20. 21. 22.
23.
lar filtration rate in the first three weeks of life. J Pediatr 87:268-272, 1975 Fawer CL, Torrado A, Guignard JP: Maturation of renal function in full term and premature neonates. Helv Paediatr Acta 34:11-21, 1979 Kotchen TA, Strickland AL, Rice TW, Walters DR: A study of the renin-angiotensin system in newborn infants. J Pediatr 80:938-946, 1972 Phibbs RH: The newborn infant. In Rudolph AM (ed): Pediatrics. Norwalk, CT: Appleton-Century-Crofts, 1982, pp 130-131 Volpe M, Odell G, Kleinert HD, Miller F, Camargo MJ, Laragh JH, Maack T, Vaughan ED, Atlas SA: Effect of atrial natriuretic factor on blood pressure, renin, and aldosterone in Goldblatt hypertension. Hypertension 7 (Suppl I):I43-I48, 1985 Laragh JH: Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure-electrolyte homeostasis. N Engl J Med 313:1330-1340, 1985
Downloaded by: NYU. Copyrighted material.
12. Maack T, Atlas SA, Camargo MJF, Cogan MG: Renal hemodynamic and natriuretic effects of atrial natriuretic factor. Fed Proc 45:2128-2132, 1985 13. Atlas SA, Volpe M, Sosa RE, Laragh JH, Camargo MJF: Effects of atrial natriuretic factor on blood pressure and the renin-angiotensin-aldosterone system. Fed Proc 45: 2115-2121, 1986 14. Antonipillai L, Vogelsang J, Horton R: Role of atrial natriuretic factor in renin release. Endocrinology 119:318322, 1986 15. Vari RC, Freeman RH, Davis JO, Villarreal D, Verburg KM: Effect of synthethic atrial natriuretic factor on aldosterone secretion in the rat. Am J Physiol 251(lPt2):R4852, 1986 16. Elliott ME, Goodfriend TL: Inhibition of aldosterone synthesis by atrial natriuretic factor. Fed Proc 45:2376— 2381, 1986 17. Kleinman LI: Developmental renal physiology. Physiologist 25:104-110, 1981 18. Guignard JP, Torrado A, DaCunha O, Gautier E: Glomeru-
177
