Plasma prorenin: Cryoactivation and relationship to renin substrate in normal subjects

      This paper is only available as a PDF. To read, Please Download here.


      We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity.
      In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active reninlike material at -5 °C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from −5 ° to +4 °C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activation of prorenin most likely occurs in all routine renin assays.
      The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma.
      In a group of 23 normal subjects with plasma renin activity of 3.5 ± 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 ± 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p < 0.001). When the actual “concentration” of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p < 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Goldblatt H
        • Haas E
        Renal mechanism in hypertension.
        in: Metcott J Proceedings of the 6th Annual Conference on Nephrotic Syndrome. National Nephrosis Foundation, Inc, New York1955: 117
        • Haas E
        • Lamfrom H
        • Goldblatt H
        Ultraviolet spectroscopy of renin.
        Arch Biochem Biophys. 1953; 44: 79
        • Skeggs LT
        • Lentz KE
        • Kahn JR
        • et al.
        Multiple forms of human kidney renin.
        in: Genest J Koiw E Hypertension 1972. Springer-Verlag, Berlin-Heidelberg-New York1972: 149
        • Newsome HH
        Purification of bovine renin.
        Biochim Biophys Acta. 1959; 185: 247
        • Rubin L
        Purification of hog renin. Properties of purified hog renin.
        Scand J Lab Invest. 1972; 29: 51
        • Lumbers ER
        Activation of renin in human amniotic fluid by low pH.
        Enzymologia. 1971; 40: 329
        • Boyd W
        A protein-bound form of porcine renal renin.
        Circ Res. 1974; 35: 426
        • Leckie B
        Activation of a possible zymogen of renin in rabbit kidney.
        Clin Sci. 1973; 44: 301
        • Day RP
        • Luetscher JA
        • Zager PG
        Big renin: identification, chemical properties and clinical implications.
        Am J Cardiol. 1976; 37: 667
        • Inagami T
        • Murakami K
        Purification of renin precursor from hog kidney.
        Circulation. 1975; 51, 52 (abstract): 14
        • Skinner SL
        • Cran EJ
        • Gibson R
        • et al.
        Angiotensins I and II, active and inactive renin, renin substrate, renin activity and angiotensinase in human liquor amnii and plasma.
        Am J Obstet Gynecol. 1975; 121: 626
        • Osmond DH
        • Ross U
        • Sciaff KD
        Increased renin activity after cold storage of human plasma.
        Can J Physiol Pharmacol. 1973; 51: 705
        • Sealey JE
        • Laragh JH
        “Prorenin” in human plasma.
        Circ Res. 1975; 36, 37: 10
        • Sealey JE
        • White RW
        • Laragh JH
        • et al.
        Plasma prorenin in anephric patients.
        Circ Res. 1976; (suppl) (in press)
        • Sealey JE
        • Gerten-Banes J
        • Laragh JH
        The renin system: variations in man measured by radioimmunoassay or bioassay.
        Kidney Int. 1972; 1: 240
        • Sealey JE
        • Laragh JH
        Radioimmunoassay of plasma renin activity.
        in: Semin Nucl Med. 5. 1975: 189
        • Haas E
        • Goldblatt H
        • Gipson EC
        Extraction, purification and acetylation of human renin and the production of antirenin to human renin.
        Arch Biochem Biophys. 1965; 110: 534
        • Pickens PT
        • Bumpus F
        • Merlin F
        • et al.
        Measurement of renin activity in human plasma.
        Circ Res. 1965; 17: 438
        • Sealey JE
        • Laragh JH
        Searching out low renin patients. Limitations of some commonly used methods.
        Am J Med. 1973; 55: 303
        • Newton MA
        • Sealey JE
        • Ledingham JGG
        • et al.
        High blood pressure and oral contraceptives.
        Am J Obstet Gynecol. 1968; 101: 1037
        • Irias JJ
        • Olmstead MR
        • Utter MF
        Pyruvate carboxylase. Reversible inactivation by cold.
        Biochemistry. 1969; 8: 5136
        • Jarabak J
        • Seeds Jr, AE
        • Talalay P
        Reversible cold inactivation of a 17β-hydroxysteroid dehydrogenase of human placenta; protective effect of glycerol.
        Biochemistry. 1966; 5: 1269