Renin inhibition: A novel therapy for cardiovascular disease

American Heart Journal

Volumn 131, Issue 5, 1996, Pages 1024-1034

  Lin, Cherry ^a   Frishman, William H ^a,b  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [3 [1 CYCLOHEXYLMETHYL 2 HYDROXY 3 [(1 METHYL 5 TETRAZOLYL)THIO]PROPYL]UREIDO] 1 METHYL 5 PHENYL 2,3 DIHYDRO 1H 1,4 BENZODIAZEPIN 2 ONE; 4 CYCLOHEXYL 2 HYDROXY 3 [N [3 (MORPHOLINOCARBONYL) 2 (1 NAPHTHYLMETHYL)PROPIONYL]HISTIDYLAMINO]BUTYRIC ACID ISOPROPYL ESTER; A 74273; ANGIOTENSIN; ANGIOTENSINOGEN; ANGIOTENSINOGEN DERIVATIVE; BRADYKININ; CGP 38560; CI 992; CIPROKIREN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALKIREN; H 142; N BENZYLOXYCARBONYLARGINYLARGINYLPROLYLPHENYLALANYLHISTIDYLSTATINYLISOLEUCYLHISTIDYL (NEPSILON BUTYLOXYCARBONYLLYSINE) METHYL ESTER; N MORPHOLINOACETYL[3 (1 NAPHTHYL)ALANYL][3 (4 THIAZOLYL)ALANYL] 4 AMINO 5 CYCLOHEXYL 3 HYDROXYPENTANOIC ACID HEXYLAMIDE; NALPHA [3 MORPHOLINOCARBONYL 2 (1 NAPHTHYLMETHYL)PROPIONYL]HISTIDINE N [1 CYCLOHEXYLMETHYL 2 HYDROXY 3 (1 METHYL 5 TETRAZOLYLTHIO)PROPYL]AMIDE; PEPSTATIN DERIVATIVE; PRORENIN; PROSTAGLANDIN; REMIKIREN; RENIN; RENIN ANTIBODY; RENIN INHIBITOR; SR 43845; STATIN; UNCLASSIFIED DRUG; ZANKIREN;

BLOOD PRESSURE REGULATION; BLOOD VESSEL TONE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DIARRHEA; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG POTENTIATION; ESSENTIAL HYPERTENSION; HEART PALPITATION; HUMAN; HYPOTENSION; INTRAPERITONEAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; MALAISE; NOCTURIA; NONHUMAN; ORAL DRUG ADMINISTRATION; PLASMA RENIN ACTIVITY; PRIORITY JOURNAL; RASH; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; TRANSDERMAL DRUG ADMINISTRATION; VERTIGO;

EID: 0029970514     PISSN: 00028703     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0002-8703(96)90190-8     Document Type: Article

References (116)

1. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee, Fifth Report. Arch Intern Med 1993;153:154-83.
2. Dzau VJ, Burt DW, Pratt RE. Molecular biology of the reninangiotensin system. Am J Physiol 1988;255:F563-73.
3. Baxter JD, James MN, Chu WN, Duncan K, Haider MA, Carilli CT, Reudelhuber TL. The molecular biology of human renin and its gene. Yale J Biol Med 1989;62:493-501.
4. Pratt RT, Onelette AJ, Dzau VJ. Biosynthesis of renin: multiplicity of active and intermediate forms. Proc Natl Acad Sci USA 1983;80:6809-13.
5. Galen FX, Corvol MT, Devaux C, GublerMC, Mounier F, Camilleri JP, Houot AM, Menard J, Corvol P. Renin biosynthesis by human tumoral juxtaglomerular cells: evidence for a renin precursor. J Clin Invest 1984;73:1144-55.
6. Corvol P, Chauveau D, Jeunemaitre X, Menard J. Human renin inhibitor peptides. Hypertension 1990;16(1):1-11.
7. Derkx FHM, Wenting EJ, Man IN, Veld AJ, Verhoeven RP, Schalekamp MADH. Control of enzymatically inactive renin in man under various pathological conditions: implications for the interpretation of renin measurements in peripheral and renal venous plasma. Clin Sci Mol Med 1978;54:529-38.
8. Clauser E, Gaillard I, Wei L, Corvol P. Regulation of angiotensinogen gene. Am J Hypertens 1989;2:403-10.
9. Tewksbury DA, Dart RA, Travis J. The amino terminal amino acid sequence of human angiotensinogen. Biochem Biophys Res Commun 1981;99:1311-5.
10. Kageyama R, Ohkubo M, Nakanishi S. Primary structure of human preangiotensuiogen deduced from the cloned cDNA sequence. Biochemistry 1984;23:3603-9.
11. Skeggs LT, Lentz KE, Kahn JR, Hochstrasser H. Kinetics of the reaction of renin with nine synthetic peptide substrates. J Exp Med 1968;128:13-34.
12. Cushman DW, Ondetti MA. Inhibitors of angiotensin converting enzyme. In: Ellis GP, West GB, eds. Progress in medicinal chemistry. Amsterdam: Elsevier/North Holland Biomedical Press, 1980:42-104.
13. Hahn AWA, Resnik TJ, Scott-Barden T, Powell J, Dohi Y, Buler FR. Stimulation of endothelin mRNA and secretion in rat vascular smooth muscle cells: a novel autocrine function. Cell Reg 1990;1:649-59.
14. Ferrario CM. The renin angiotensin system: importance in physiology and pathology. J Cardiovasc Pharmacol 1990;15(suppl 3):S1-S5.
15. Tewksbury DA. Angiotensinogen: biochemistry and molecular biology. In: Laragh JH, Brenner BM, eds. Hypertension: pathophysiology, diagnosis and management. New York: Raven Press, 1990:1197-216.
16. Johnson CA, Wakerlin GE. Antiserum for renin. Proc Soc Exp Biol Med 1940;44:277-81.
17. Deodhar SD, Haas E, Goldblatt H. Production of antirenin to homologous renin and its effect on experimental renal hypertension. J Exp Med 1964;119:425-32.
18. Helmer OM. Studies on renin antibodies. Circulation 1958;17:648-52.
19. Dzau VJ, Kopelman RI, Barger AC, Haber E. Renin-specific antibody for study of cardiovascular homeostasis. Science 1980;207:1091-3.
20. Wood JM, Baum HP, Bews JPA, Wachsmuth ED, Heusser C, Hofbauer KG. Effects of chronic administration of a monoclonal antibody against human renin in the marmoset. Clin Exp Hypertens [A] 1987;A9:1467-78.
21. Wood JM, Heusser C, Gulati N, Forgiarini P, Hofbaur KG. Monoclonal antibodies against human renin: blood pressure effects in the marmoset. Hypertension 1986;8:600-5.
22. Evin G, Devin J, Castro B, Menard J, Corval P. Synthesis of peptides related to the prosegment of mouse submaxillary gland renin precursor: an approach to renin inhibitors. Proc Natl Acad Sci USA 1984; 81:48-52.
23. Cumin F, Evin G, Fehrentz JA, Seyer R, Castro B, Menard J, Corval P. Inhibition of human renin by synthetic peptides derived from its prosegment. J Biol Chem 1985;260:9154-7.
24. Aoyagi T, Kunimoto S, Morishima H, Takauchi T, Umazawa H. Effect of pepstatin on acid proteases. J Antibiotic (Tokyo) 1971;24:687-94.
25. Gross F, Lazar J, Orth H. Inhibition of renin-angiotensinogen reaction by pepstatin. Science 1972;175:656.
26. Miller RP, Poper CJ, Wilson CW, Devito E. Renin inhibition by pepstatin. Biochem Pharmacol 1972;21:2941-4.
27. Boger J, Lohr NS, Ulm EH, Poe M, Blaine EH, Fanelli GM, Lin TY, Payne LS, Schorn TW, LaMont BI, Vassil TC, Stabilito II, Veber DF, Rich DH, Bopari AS. Novel renin inhibitors containing the amino acid statine. Nature 1983;303:81-4.
28. Guegan R, Diaz J, Cazaubon C, Beaumont M, Carlet C, Clement J, Demarne H, Mellet M, Richaud JP, Segondy D, Vedel M, Gagnol JP, Roncucci R, Castro B, Corvol P, Evin G, Roques B. Pepstatin analogues as novel renin inhibitors. J Med Chem 1986;29(7):1152-9.
29. Rich DH, Bernatowicz MS, Agarwal NS, Kawai M, Salituro FG, Schmidt PG. Inhibition of aspartic protease by pepstatin and 3-methyl statine derivatives of pepstatin: evidence for collected substrate enzyme inhibition. Biochemistry 1985;24:3165-73.
30. Kokubu T, Ueda E, Fujimoto S. Peptide inhibitor of the renin angio-tensin system. Nature 1968;217:456-7.
31. Poulsen K, Burton J, Haber E. Competitive inhibitors of renin. Biochemistry 1973;12:3877-82.
32. Burton J, Cody RJ, Herd AJ, Haber E. Specific inhibition of renin by an angiotensinogen analogue: studies in sodium depletion and renindependent hypertension. Proc Natl Acad Sci USA 1980;77:5476-9.
33. Zusman RM, Burton J, Christensen D, Nussberger J, Dodds A, Haber E. Hemodynamic effects of a competitive renin inhibitory peptide in humans: evidence for multiple mechanisms of action. Trans Am Assoc Physicians 1983;96:365-74.
34. Szelke M, Leckie BJ, Hallett A, Jones M, Sueiras J, Astrash B, Lever AF. Potent new inhibitors of human renin. Nature 1982;299:555-7.
35. Kokubu T, Hiwada K, Nagae A, Murakami E, Morisawa Y, Yabe Y, Koike H, Iijima Y. Statine-containing dipeptide and tripeptide inhibitors of human renin. Hypertension 1986;8(suppl II):II-1-5.
36. Kokubu T, Hiwada K, Murakami E, Muneta S. In vitro inhibition of human renin by statine-containing tripeptide renin inhibitor (ES 1005). J Cardiovasc Pharmacol 1987;10(suppl 7):S88-90.
37. Bock MG, Diapardo RM, Evans BE, Rittle KE. Renin inhibitors: statine-containing tetrapeptides with varied hydrophobic carboxy terminal. J Med Chem 1987;30(10):1853-7.
38. Iizuka J, Kamijo T, Kubota T, Akahane K, Umeyama H, Kiso Y. New human renin inhibitors containing an unnatural amino acid, norstatine. J Med Chem 1988;31:701-4.
39. Toda N, Miyazoki M, Etoh Y, Kubota T, Ilzuka K. Human renin inhibiting dipeptide. Eur J Pharmacol 1986;129:393-6.
40. Thaisrivongs S, Pals DT, Kati WM, Turner SR, Thomasco LM. Difluorostatine and difluorstatone containing peptides as potent and specific renin inhibitors. J Med Chem 1985;28:1553-5.
41. Thairsrivongs S, Pals DT, Kati WM, Turner SR, Thomasco LM, Watt W. Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone and related analogues. J Med Chem 1986;29(10):2080-7.
42. Boger J, Payen LS, Perlow DS, Lohr NS, Poe M, Blain EH, Ulm EH, Schorn TW, LaMont BI, Lin TY, Kawai M, Rich DH, Veber DF. Renin inhibitors: syntheses of subnanomolar competitive transition-state analogue inhibitors containing a novel analogue of statine. J Med Chem 1985;28(12):1779-86.
43. Dellaria JR, Maki RG, Bopp BA, Cohen J, Kleinert HD, Luly JR, Merits I, Plattner JJ, Stein HH. Optimization and in vivo evaluations of a series of small potent and specific renin inhibitors containing a novel Leu-Val replacement. J Med Chem 1987;30(11):2137-44.
44. Hui KY, Holtzman EJ, Quinones MA, Hollenberg NK, Haber E. Design of rat renin inhibitory peptides. J Med Chem 1988;31(9):1679-86.
45. Hiwada K, Kokubu T, Murakami K, Muneta S, Morisawa Y, Yabe Y, Koike H, Iijima Y. A highly potent and long-acting oral inhibitor of human renin. Hypertension 1988;11:708-12.
46. Luly JR, BaMaung N, Soderquist J, Fung AK, Stein H, Kleinert HD, Marcotte PA, Egan DA, Bopp B, Merits I, Bolis G, Greer J, Perun TJ, Plattner JJ. Renin inhibitors: dipeptide analogues of angiotensinogen, utilizing a dihydroxythylene transition-state mimic at the scissile bond to impart greater inhibitory potency. J Med Chem 1988; 31(12):2264-76.
47. Kleinert HD, Luly TR, Marcotte PA, Perun TJ, Plattner JJ, Stein H. Renin inhibitors: improvements in the stability and biological activity of small peptides containing novel Leu-Val replacements. FEBS Lett 1988;230(1-2):38-42.
48. Kemph DJ, Delara E, Stein HH, Cohen J, Plattner JJ. Renin inhibitors based on novel dipeptide analogues: incorporation of the dehydroxyethylene isostere at the scissile bond. J Med Chem 1987; 30(11):1978-83.
49. Allen MC, Fuhrer W, Tuck B, Wade R, Wood JM. Renin inhibitors: synthesis of transition state analogue inhibitors containing phosphorus acid derivatives at the scissile bond. J Med Chem 1989;32(7):1652-61.
50. Evin G, Devin J, Castro B, Corvol P, Guegan R, Diaz J, Demarne M, Gagnol JP. New potent inhibitors of human renin. In: Hruby VJ, Rich DH, eds. Peptides: structure and function. Proceedings of the 8th American Peptide Symposium. Rockford, Illinois: Pieree Chemical Co., 1983:583-90.
51. 2NH] Val substitutions. J Med Chem 1988;31(1):18-30.
52. Haber E, Hui KY, Carlson WD, Bernatowicz MS. Renin inhibitors: a search for principles of design. J Cardiovasc Pharmacol 1987;10(suppl 7):S54-8.
53. Bock MG, Dipardo RM, Evans BE, Freidinger RM, Rittle KE, Payeu LS, Boger J, Whitter WL, LaMont BI, Ulm EH, Blaine EH, Schorn TW, Veber DF. Renin inhibitors containing hydrophilic groups: tetrapeptides with enhanced aqueous solubility and nanomolar potency. J Med Chem 1988;31:1918-23.
54. Glassman HN, Kleinert HD, Boger RS, Moyse DM, Griffiths AN, Luter RR. Clinical pharmacology of enalkiren, a novel dipeptide renin inhibitor. J Cardiovasc Pharmacol 1990;16(suppl 40):S76-81.
55. De Gasparo M, Cumin F, Nussberger J, Guyenne TT, Wood JM, Menard J. Pharmacological investigation of a new renin inhibitor in normal sodium-unrestricted volunteers. Br J Clin Pharmacol 1989; 27(5):587-96.
56. Boyd SA, Fung AKL, Baker WR, Mantei RA, Armiger Y-L, Stein HH, Cohen J, Egan DA, Barlow JL, Klinghofer V, Verburg KM, Martin DL, Young GA, Polakowski JS, Hoffman DJ, Garren KW, Perun TJ, Kleinert HD. C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties. J Med Chem 1992;35:1735-46.
57. Sham HL, Bolis G, Stein HH, Fesik SW, Marcotte PA, Plattner JJ, Rempel CA, Greer J. Renin inhibitors: design and synthesis of a new class of conformationally restricted analogues of angiotensinogen. J Med Chem 1988;31(2):284-95.
58. Webb DJ, Manhem PJ, Ball SG, Inglis G, Leckie BJ, Lever AF, Morton JJ, Robertson JI, Murray GD, Menard J, Semple PF, Szelke M. A study of the renin inhibitor H-142 in man. J Hypertens 1985;3:653-8.
59. Blaine EH, Schorn TW, Boger J. Statine-containing renin inhibitor: dissociation of blood pressure lowering and renin inhibition in sodium-deficient dogs. Hypertension 1984;6(suppl I):I111-8.
60. Wood JM, Baum HP, Jobber RA, Neisius D. Sustained reduction in blood pressure during chronic administration of a renin inhibitor in normotensive marmosets. J Cardiovasc Pharmacol 1987;10(suppl 7):S96-8.
61. LaCour C, Cazaubon C, Roccon A, Segondy D, Wagnon J, Nisato D. Effects of a renin inhibitor SR 43845 and of captopril on blood pressure and plasma active renin in conscious sodium-replete macaca. J Hypertens 1989;2(suppl 7):S33-5.
62. Jeunemaitre X, Menard J, Nussberger J, Guyene TT, Brunner HR, Corvol P. Plasma angiotensinogens, renin and blood pressure during acute renin inhibition by CGP-385560A in hypertensive patients. Am J Hypertens 1989;2:819-27.
63. Weber MA, Neutel JM, Essinger J, Glassman HN, Boger RS, Luther R. Assessment of renin dependency of hypertension with a dipeptide renin inhibitor. Circulation 1990;81(6): 1768-74.
64. Kleinert HD, Martin D, Chekal MA, Kadam J, Luly JR, Plattner JJ, Perun TJ, Luther RR. Effects of the renin inhibitor A-64662 in monkeys and rats with varying baseline plasma renin activity. Hypertension 1988;11:613-9.
65. Gupta SK, Granneman GR, Packer M, Boger RS. Simultaneous modeling of the pharniacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a renin inhibitor). II: A dose-ranging study in patients with congestive heart failure. J Cardiovasc Pharmacol 1993;21(5):834-40.
66. Fisher N, Cordero P, Moore TJ, Williams GH, Hollenberg NK. Renal and endocrine responses to a renin inhibitor (RIP) in normal humans on a 10 mEq NaCl intake. J Hypertens 1990;8(suppl 3):S13.
67. Jackson B, Liu G, Perich RB, Paxton D, McNicols L, Gutteridge G, Johnston CI. Haemodynamic, renal and hormonal responses to enalkiren in four patients with post-surgical oliguria. Proceedings of the HBPRCA. Clin Exp Pharmacol Physiol 1994;21:163-6.
68. Gupta SK, Granneman GR, Boger RS, Hollenberg NK, Luther RR. Simultaneous modeling of the pharniacokinetic and pharmacodynamic properties of enalkiren (Abbott-64662, a new renin inhibitor). I: Single dose study. Drug Metab Dispos 1992;20(6):821-5.
69. Kleinert HD, Luly JR, Bopp BA, Verburg KM, Hoyos PA, Kard MD, Plattner JJ, Luther RR, Stein HH. Profile of the renin inhibitor, enalkiren (ABBOTT-64662). Cardiovasc Drug Rev 1990;8:203-19.
70. Delabays A, Nussberger J, Porchet M, Waeber B, Hoyos P, Boger R, Glassman H, Kleinert H, Luther R, Brunner H. Hemodynamic and humoral effects of the new renin inhibitor enalkiren in normal humans. Hypertension 1989;13:941-7.
71. Griffths AN, Neutel JM, Glassman HN, Boger RS, Weber MA, Luther RR. The hypotensive effect of increasing doses of enalkiren, a dipeptide renin inhibitor, compared with enalaprilat in hypertensive patients. Br J Clin Pharmacol 1990;29:614P-5P.
72. Anderson PW, Do YS, Schambelan M, Horton R, Boger RS, Luther RR, Hsueh WA. Effects of renin inhibition in systemic hypertension. Am J Cardiol 1990;66:1342-7.
73. Neutel JM, Luther RR, Boger RS, Weber MA. Immediate blood pressure effects of the renin inhibitor enalkiren and the angiotensin-converting enzyme inhibitor enalaprilat. AM HEART J 1991;122:1094-100.
74. Bursztyn M, Gavras I, Tifft CP, Bauer JH, Melby JC, Gavras H. Renin inhibition with A-64662: effect in blood pressure and hormonal response in man. J Hypertens 1989;7(suppl):S306-7.
75. Boger RS, Glassman HN, Cavanaugh JH, Schmitz PJ, Lamm J, Moyse D, Cohen A, Kleinhart H, Luther RR. Prolonged duration of blood pressure response to enalkiren, the novel dipeptide renin inhibitor, in essential hypertension. Hypertension 1990;15(6, Part 2):835-40.
76. Haber E. Why renin inhibitors? J Hypertens 1989;7(suppl 2):S81-6.
77. Kleinert HD, Rosenberg SH, Baker WR, Stein HH, Klinghofer V, Barlow J, Spina K, Polakowski J, Kover P, Cohen J, Denissen J. Discovery of a peptide based renin inhibitor with oral bioavailability and efficacy. Science 1992;257:1940-3.
78. Rosenberg SH, Spina KP, Woods KW, Polakowski J, Martin DL, Yao Z, Stein HH, Cohen J, Barlow JL, Egan DA, Tricarico KA, Baker WR, Kleinert HD. Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides. J Med Chem 1993;36:449-59.
79. Wessale JL, Kleinert HD, Calzadilla SV, Kovar PJ, Rosenberg SH. Effects of renin inhibitor A-72517 on hemodynamics and cardiac function in sodium-depleted dogs. Am J Hypertens 1993;6:514-21.
80. Menard J, Boger RS, Moyse DM, Guyene TT, Glassman HN, Kleinert HD. Dose-dependent effects of the renin inhibitor zankiren HCl after a single oral dose in mildly sodium-depleted normotensive subjects. Circulation 1995;91(2):330-8.
81. Kleinert HD, Stein HH, Boyd S, Fung AKL, Baker WR, Verburg KM, Polakowski JS, Kovar P, Barlow J, Cohen J, Klinghofer V, Mantel R, Cepa S, Rosenberg S, Denissen JF. Discovery of well absorbed, efficacious renin inhibitor, A-74273. Hypertension 1992;30:768-75.
82. Verburg KM, Plakowski JS, Kovar PJ, Klinghofer V, Barlow JL, Stein HH, Mantel RA, Fung AKL, Boyd SA, Baker WR, Kleinert HD. Effects of high doses of A-74273, a novel nonpeptidic and orally bioavailable renin inhibitor. J Cardiovasc Pharmacol 1993;21(1):149-55.
83. van Paassen P, de Zeeuw D, de Jong PE. Renal and systemic effects of the renin inhibitor remikiren in patients with essential hypertension. J Cardiovasc Pharmacol 1995;26:39-45.
84. Kleinbloesem CH, Weber C, Fahrner E, Dellenbach M, Welker H, Schroter V, Belz GG. Hemodynamics, biochemical effects, and pharmacokinetics of the renin inhibitor remikiren in healthy human subjects. Clin Pharmacol Ther 1993;53(5):585-92.
85. Greenlee WJ, Weber AE. Renin inhibitors. Drug News Perspect 1991;4:332-9.
86. Camenzino E, Nussberger J, Juillert L, Munafo A, Fischli W, Coussolo P, van Brumelen P, Kleinbloesem CH, Waeber B, Brunner HR. Effects of the renin response during renin inhibition: oral Ro 42-5892 in normal humans. J Cardiovasc Pharmacol 1991;18:299-307.
87. Clozel JP, Fischli W. Comparative effects of three different potent renin inhibitors in primates. Hypertension 1993;22(1):9-17.
88. Kobrin I, Viskoper RJ, Laszt A, Bock J, Weber C, Charlon V. Effects of an orally active renin inhibitor Ro 42-5892, in patients with essential hypertension. Am J Hypertens 1993;6:349-56.
89. Van den Meiracker AH, Admiraal PJ, Man in't Veld AJ, Derkx FH, Ritsema van Eck HJ, Mulder P, van Brummelen P, Schalekamp MA. Prolonged blood pressure reduction by orally active renin inhibitor Ro 42-5892 in essential hypertension. BMJ 1990;301:205-10.
90. Doig JK, MacFadyen RJ, Meredith PA, Fischli W, Reid JL. Neurohormonal and blood pressure responses to low-dose infusion of an orally active renin inhibitor, Ro 42-5892 in salt replete men. J Cardiovasc Pharmacol 1992;20:875-80.
91. Fischli W, Clozel JP, Breu V, Buchmann S, Mathews S, Stadler H, Vieira E, Wostl W. Ciprokiren (Ro 44-9375): a renin inhibitor with increasing effects on chronic treatment. Hypertension 1994;24(2): 163-9.
92. Etoh Y, Miyazaki M, Saitoh H, Toda N. KRI-1314: an orally effective inhibitor of human renin. Jpn J Pharmacol 1993;63:109-19.
93. Shibasaki M, Asano M, Fukunaga Y, Usui T, Ichihara M, Murakami Y, Nakano K, Fujikura T. Pharmacological properties of YM-21095, a potent and highly specific renin inhibitor. Am J Hypertens 1991; 4:932-8.
94. Shibasaki M, Usui T, Inagaki O, Asano M, Takenaka T. Pharmakinetics and cardiovascular effects of YM-21095, a novel renin inhibitor, in dogs and monkeys. J Pharm Pharmacol 1994;46(1):68-72.
95. Shibasaki M, Shibasaki K, Ichihara M, Inagaki O, Yanagisawa I, Takenaka T, Murakami K. Pharmacological properties of YM-26365, a low molecular weight, orally active renin inhibitor. Eur J Pharmacol 1994;271:341-8.
96. Ii Y, Murakami E, Hiwada K. Effect of renin inhibitor, ES-8891, on renal renin secretion and storage in the marmoset: comparison with captopril. J Hypertens 1991;9:1119-25.
97. Ryan MJ, Hicks GW, Batley BL, Rapundalo ST, Patt WC, Taylor DG, Keiser JA. Effect of an orally active renin inhibitor C1-992 on blood pressure in normotensive and hypertensive monkeys. J Pharmacol Exp Ther 1994;268(1):372-9.
98. Dzau VJ. Tissue renin angiotensin system: physiologic and pharmacologie implications. Circulation 1988;77(6, suppl I):I1-3.
99. Schaffer LW, Winquist RJ, Siegl PKS. Hypotensive effect of inhibition of renin and converting enzyme in normotensive African green mon-keys. FASEB J 1988;2(4):A605.
100. DeClaviere M, Fourment P, Richaud JP, Unkovic J, Gagnol JP, Mazue G. Haeniodynamic effects of the renin inhibitor SR 42128 in conscious baboon. J Hypertens 1985;3(suppl 3):S271-3.
101. Kleinert HD, Martin D, Chekal M, Young G, Rosenberg S, Plattner JJ, Perun TJ. Cardiovascular actions of the primate selective renin inhibitor A-62198. J Pharmacol Exp Ther 1988;246:975-9.
102. Hofbauer KG, Wood JM, Gulati N, Heusser C, Menard J. Increased plasma renin during renin inhibition: studies with a novel immunoassay. Hypertension 1985;7(suppl I):I61-5.
103. Mento PF, Holt WF, Murphy WR, Wilkes BM. Combined renin and converting enzyme inhibition in rats. Hypertension 1989;13:741-8.
104. Blaine EH, Nelson EJ, SeymourAA, Schorn TW, Sweet CS, Slater EE, Nussberger J, Boger J. Comparison of renin and converting enzyme inhibition in sodium-deficient dogs. Hypertension 1985;7(suppl I):I66-71.
105. Fossa AA, Weinberg LJ, Barber RL, Rauch AL, Nocerini MR, Murphy WR, Swindell AC. Synergistic effect on reduction in blood pressure with coadministration of the renin inhibitor, CP-80,794, and the angiotensin converting enzyme inhibitor, captopril. J Cardiovasc Pharmacol 1992;20(1):75-82.
106. Smith SG, Seymour AA, Mazack EK, Boger J, Blaine EH. Comparison of a new renin inhibitor and enalapril in renal hypertensive dogs. Hypertension 1987;9(2):150-6.
107. Meisius D, Wood JM. Antihypertensive effect of a renin inhibitor in marmosets with a segmental renal infarction. J Hypertens 1987; 5(6):721-5.
108. Sweet CS, Ludden CT, Frederick CM, Bush LR, Riberro LGT. Comparative hemodynamic effects of MK-422, a converting enzyme inhibitor, and a renin inhibitor in dogs with acute left ventricular failure. J Cardiovasc Pharmacol 1984;6(6):1067-75.
109. Gavras I, Cannon PJ, Brunner HR, Laragh JH. Is elevated plasma renin activity of prognostic importance in progressive systemic sclerosis? Arch Intern Med 1977;137:1554-8.
110. Laragh JH, Baer L, Brunner HR, Buhler FR, Sealey JE, Vaughn ED Jr. Renin, angiotensin, and aldosterone system in pathogenesis and management of hypertensive vascular disease. Am J Med 1972;52:633-52.
111. Laragh JH. The renin system and four lines of hypertension research: nephron heterogeneity, the calcium connection, and the prorenin vasodilator limb and plasma renin and heart attack. Hypertension 1992;20:267-79.
112. Giardina WJ, Kleinert HD, Ebert DM, Wismer CT, Chekal MA, Stein HH. Intraocular pressure lowering effects of the renin inhibitor Abbott-64662 diacetate in animals. J Ocul Pharmacol 1990;6(2):75-83.
113. Bursztyn M, Gavras I, Tifft CP, Luther R, Boger R, Gavras H. Effects of a novel renin inhibitor in patients with essential hypertension. J Cardiovasc Pharmacol 1990;15:493-500.
114. Ondetti MA, Cushman DW. Inhibition of the renin angiotensin system: a new approach to the therapy of hypertension. J Med Chem 1981;24:355-61.
115. Tewksbury DA, Dart RA, Travis J. The amino terminal amino acid sequence of human angiotensinogen. Biochem Biophys Res Commun 1981;99:1311-5.
116. Hofbauer KG, Wood JM, Gulati N, Heusser C, Menard J. Increased plasma renin during renin inhibition: studies with a novel immunoassay. Hypertension 1985;7(suppl I):I61-5.