Abstract
Natriuretic peptides have not only natriuretic/diuretic but also hypotensive activities, and the decreased renal perfusion caused by the excessive hypotension is known to attenuate the diuretic actions. The present study was designed to examine the relationship between the dosing (intravenous constant infusion) rates and the diuretic actions of α-rat atrial natriuretic peptide (α-rANP) and rat brain natriuretic peptide (rBNP) in rats, and population (nonlinear mixed effect model) analysis was applied to these complicated diuretic actions. The intrinsic diuretic activities of α-rANP and rBNP could be analyzed, and the effects of blood pressure, heart rate, and also inhibition of degradation enzyme on the diuresis of natriuretic peptides were estimated simultaneously. The population analysis was useful for analyzing such pharmacodynamic data for which the individual analysis could not be applied easily.
Similar content being viewed by others
References
Y. Saito, K. Nakao, K. Nishimura, A. Sugawara, K. Okumura, K. Obata, R. Sonoda, T. Ban, H. Yasue, and H. Imura. Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function.Circulation 76:115–124 (1987).
T. D. Giles, A. C. Quiros, L. E. Roffidal, H. Marder, and G. E. Sander. Prolonged hemodynamic benefits from a high-dose bolus injection of human atrial netriuretic factor in congestive heart failure.Clin. Pharmacol. Ther. 50:557–563 (1991).
P. Needleman, E. H. Blaine, J. E. Greenwald, M. L. Michener, C. B. Saper, P. T. Stockmann, and H. E. Tolunary. The biochemical pharmacology of atrial peptides.Ann. Rev. Pharmacol. Toxicol. 29:23–54 (1989).
E. H. Blaine, Atrial natriuretic factor plays a significant role in body fluid homeostasis.Hypertension 15:2–8 (1990).
T. Sudoh, K. Kangawa, N. Minamino, and H. Matsuo. A new natriuretic peptide in porcine brain.Nature 332:78–81 (1988).
Y. Saito, K. Nakao, H. Itoh, I. Yamada, M. Mukoyama, K. Arai, K. Hosoda, G. Shirakami, S. Suga, N. Minamino, K. Kangawa, H. Matsuo, and H. Imura. Brain natriuretic peptide is a novel cardiac hormone.Biochem. Biophys. Res. Commun. 161:732–739 (1989).
Y. Ogawa, K. Nakao, M. Mukoyama, G. Shirakami, H. Itoh, K. Hosoda, Y. Saito, H. Arai, S. Suga, M. Jougasaki, T. Yamada, Y. Kambayashi, K. Inouye, and H. Imura. Rat brain natriuretic peptide-tissue distribution and molecular form.Endocrinology 126:2225–2227 (1990).
Y. Kambayashi, K. Nakao, M. Mukoyama, Y. Saito, Y. Ogawa, S. Shiono, K. Inouye, N. Yoshida, and H. Imura. Isolation and sequence determination of human brain natriuretic peptide in human atrium.FEBS Lett. 259:341–345 (1990).
S. L. Beal and L. B. Sheiner (eds.).NONMEM Users Guides, NONMEM Project Group, University of California at San Francisco, San Francisco, 1989.
L. B. Sheiner and T. M. Ludden. Population pharmacokinetics/dynamics.Ann. Rev. Pharmacol. Toxicol. 32:185–209 (1992).
A. J. Kenny and A. L. Stephenson. Role of endopeptidase-24.11 in the inactivation of atrial natriuretic peptide.FEBS Lett. 232:1–8 (1988).
R. L. Webb, G. D. Yasay, C. McMartin, R. B. McNeal, and M. B. Zimmerman. Degradation of atrial natriuretic peptide: pharmacologie effects of protease EC 24.11 inhibition.J. Cardiovasc. Pharmacol. 14:285–293 (1989).
Y. Kambayashi, K. Nakao, H. Kimura, T. Kawabata, M. Nakamura, K. Inouye, N. Yoshida, and H. Imura. Biological characterization of human brain natriuretic peptide (BNP) and rat BNP: species-specific actions of BNP.Biochem. Biophys. Res. Commun. 173:599–605 (1990).
M. Yoshimura, H. Yasue, E. Morita, N. Sakaino, M. Jougasaki, M. Kurose, M. Mukoyama, Y. Saito, K. Nakao, and H. Imura. Hemodynamic, renal and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure.Circulation 84:1581–1588 (1991).
Y. Hashimoto, K. Nakao, N. Hama, M. Mukoyama, H. Imura, M. Yasuhara, and R. Hori. Pharmacokinetics of brain natriuretic peptide in rats.Chem. Pharm. Bull. 40:1650–1652 (1992).
M. R. Wilkins, S. L. Settle, and P. Needleman. Augmentation of the natriuretic activity of exogenous and endogenous atriopeptin in rats by inhibition of guanosine 3′, 5′-cyclic monophosphate degradation.J. Clin. Invest. 85:1274–1279 (1990).
M. Chinkers, D. L. Garbers, M. S. Chang, D. G. Lowe, H. Chin, and D. V. Schulz. A membrane form of guanylate cyclase is an atrial natriuretic receptor.Nature 338:78–83 (1989).
K. J. Koller, D. G. Lowe, G. L. Bennett, N. Minamino, K. Kangawa, H. Matsuo, and D. V. Goeddel. Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP).Science 252:120–123 (1991).
S. Suga, K. Nakao, K. Hosoda, M. Mukoyama, Y. Ogawa, G. Shirakami, H. Arai, Y. Saito, Y. Kambayashi, K. Inouye, and H. Imura. Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide.Endocrinology 130:229–239 (1992).
N. Yokota, Y. Yamamoto, M. Aburaya, K. Kitamura, T. Eto, K. Kangawa, N. Minamino, H. Matsuo, and K. Tanaka. Increased secretion of brain natriuretic peptide and atrial natriuretic peptide, but not sufficient to induce natriuresis in rats with nephrotic syndrome.Biochem. Biophys. Res. Commun. 174:128–135 (1991).
T. Maack, M. Suzuki, F. A. Almeida, D. Nussenzveig, R. M. Scarborough, G. A. McEnroe, and J. A. Lewicki. Physiological role of silent receptors of atrial natriuretic factor.Science 238:675–678 (1987).
G. M. Olins, P. A. Krieter, A. J. Trapani, K. L. Spear, and P. R. Bovy. Specific inhibitors of endopeptidase 24.11 inhibit the metabolism of atrial natriuretic peptide in vitro and in vivo.Mol. Cell. Endocrinol. 61:201–208 (1989).
M. R. Wilkins, S. L. Settle, P. T. Stockmann, and P. Needleman. Maximizing the natriuretic effect of endogenous atriopeptin in a rat model of heart failure.Proc. Natl. Acad. Sci. U.S.87:6465–6469 (1990).
A. A. Seymour, M. M. Asaad, B. E. Abboa-Offei, P. L. Rovnyak, S. Fennell, and W. L. Rogers. Potentiation of brain natriuretic peptide by SQ28603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.J. Pharmacol. Exp. Ther. 262:60–70 (1992).
C. C. Lang, J. G. Motwani, W. J. R. Coutie, and A. D. Struthers. Clearance of brain natriuretic peptide in patients with chronic heart failure: indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism.Clin. Sci. 82:619–623 (1992).
M. Gagelmann, D. Hock, and W. G. Frossmann. Urodilatin (CDD/ANP95-126) is not biologically inactivated by a peptidase from dog kidney membrane in contrast to atrial natriuretic peptide/cardiodilatin (α-hANP/CDD99-126).FEBS Lett. 233:249–254 (1988).
J. A. Norman, D. Little, M. Bolgar, and D. Donata. Degradation of brain natriuretic peptide by neutral endopeptidase: species specific sites of proteolysis determined by mass spectrometry.Biochem. Biophys. Res. Commun. 175:22–30 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hashimoto, Y., Mori, S., Hama, N. et al. Nonlinear mixed effect modeling of the pharmacodynamics of natriuretic peptides in rats. Journal of Pharmacokinetics and Biopharmaceutics 21, 281–297 (1993). https://doi.org/10.1007/BF01059780
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01059780