Abstract
This study was designed to investigate the alterations in the levels of various proteases such as anglotensin converting enzyme (ACE), kallikrein, aminopeptidases, urokinase and plasmin in serum-heart and kidney and to find out whether the changes in the levels of these enzymes could explain the pathogenests of hypertension induced by Dexamethasone (Dex). Dex was administered to Male Wistar rats (180-200 g body weight) at a dosage of 2.5 mg/kg/week subcutaneously on alternate days for 2 weeks. One more week was included in this investigation to oversee the recovery process. Mean Arterial Pressure (MAP) showed significant elevation during administration and after withdrawal of Dex. The levels of enzymes such as angtotens'm converting enzyme, carboxypeptidase-N and leucine ammopeptidase were found to be elevated in serum as well as in tissues. The level of kallikrein was observed to decrease in serum and tissues and that of thrombin, plasmin and uroldnase exhibited variations. Thus, treatment with Dex altered the levels of these proteases which might have a role in the pathogenesis of hypertension and in altered blood coagulation.
Similar content being viewed by others
References
Mantero F, Boscaro M: Glucocorticold dependent hypertension. J S Steroid Biochem Mol Biol 43: 409–413, 1992
Kaplan NM: Cushing's syndrome and congenital adrenal hyperplasia. In: NM Kaplan (ed). Clinical Hypertension, Baltimore: Williams and Wilkins, 1990, pp. 386–395
Garcia LJ, Fortes ZB, Samomiya P, Farsky SP: Insulin, glucocorticolds and the control of inflammatory responses. Agents Actions suppl 36: 99–118, 1992
Aoyagi T, Wada T, Kojima F, Nagai M, Harada S, Takeuchi T: Serum protease changes in spontaneously hypertensive rats. Contrast with those in essential hypertension in man. J Clin Biochem Nutr 10: 35–40, 1991
Nolly H, Carbini LA, Scicli G, Carretero OA, Scicli AG: A local kallikrein-kinin system is present in rat hearts. Hypertension 23: 919–923, 1994
Margollus HS: Tissue kallikrein and kinins. Regulation and roles in hypertension and diabetic diseases. Annu Rev Pharmacol Toxicol 29: 343–364, 1989
Wang C, Chao L, Chao J: Direct gene delivery of human tissue kallikrein reduces blood pressure in SHR. J Clin Invest 95: 1710–1716, 1995
Fishel RS, Eisenberg S, Shai SY, Redden RA, Bemstein K, Berk BC: Glucocorticolds induce angiotensin converting enzyme expression in vascular smooth muscle. Hypertension 25: 343–349, 1995
Rapp P, Dennis LS, McPartland RP, Batten L: Hormonal effects on kallikrein, esterase A2 and their inhibitors in rat urine. Endocrinology 114: 951–956, 1984
Stefanovic V, Vlahovic P, Ardaillou N, Ardaillou R: Receptor mediated induction of aminopeptidase A of human glomerular epithelial cells by glucocorticoids. FEBS Lett 294: 171–174, 1991
Van Giezen JJJ, Jansen JWCM: Inhibition of fibrinolytic activity in vivo by Dex is counterbalanced by an inhibition of platelet aggregation. Thromb Hemostasis 68: 69–73, 1992
Nasjletti A, Erman A, Cagen LM, Baer PG: Plasma concentrations renal excretion and tissue release of prostaglandin in the rat with dexamethasone induced hypertension. Endocrinology 114: 1033–1040, 1984
Rajashree S, Puvanakrishnan R: Alterations in certain lysosomal glycohydrolases and cathepsins in rats on dexamethasone administration. Mol Cell Biochem 154: 165–170, 1996
Hayakari M, Kondo Y, Izumi H: A rapid and simple spectrophotometric assay of angiotensin converting enzyme. Anal Biochem 84: 361–369, 1978
Aoyagi T, Wada T, Kojima F, Nagai M, Umezawa H: Various enzyme activities in muscle and other organs of dystrophic mice. J Clin Invest 67: 51–59, 1981
Morita T, Kato H, Iwanaga S, Takada K, Kimura T, Sakaldbara S: New fluorogenic substrates for thrombin, factor Xa, kallikreins and urokinase. J Biochem 82: 1495–1498, 1977
Kato H, Adachi N, Ohno Y, Iwanaga S, Takada K, Sakaldbara S: New fluorogenic peptide substrates for plasmin. J Biochem 88: 183–190, 1980
Lowry OH, Rosebrough NJ, Farr AL, Randal RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951
Carretero OA, Scicli AG: The glandular kallikrein kinin system in hypertension. In: Sambht MP (ed). Fundamental fault in hypertension, Boston: Martinus Nyhoff publishers, 1984, pp. 158–174
Ito K: Glucocorticoid dependent kallikrein inhibitor in rat kidney. Chiba Igaku Zasshi 63: 197–203, 1987
Margollus HS, Horwitz D, Pisano JJ, Kelser HR: Urinary kallikrein excretion in hypertensive man. Relationship to sodium intake and sodium retaining steroids. Circ Res 35: 820–825, 1974
Zinner SH, Margollus HS, Rosner B, Kass EH: Stability of blood pressure rank and urinary kallikrein concentrations in childhood an eight year follow up. Circulation 58: 908–915, 1978
Berry TD, Hasstedt SJ, Hunt SC, Wu LL, Smith JB, Ash KO, Kuida H, Williams RR: A gene for high urinary kallikrein may protect against hypertension in Utah kindreds. Hypertension (Dallas) 13: 3–8, 1989
Ader JL, Pollock DNL Butterfield MI, Arendshorst: Abnormalities in kallikrein excretion in SHR. Am J Physiol 248: F396–F403, 1985
Argent NB, Wilkinson R, Baylis PH: Local hormones in the kidney: Protectors of the kidney against the body? J Endocrinol 126: 351–354, 1990
Dalakos TG, Elias AN, Anderson GR Streeten DHP, Schroeder ET: Evidence for an angiotensinogenic mechanism of the hypertension is Cushing's syndrome. J Clin Endocrinol Metab 46: 114–118, 1978
Dasarathy Y, Lanzillo JJ, Fanburg BL: Stimulation of bovine pulmonary artery endothelial cell ACE by dexamethasone: Involvement of steroid receptors. Am J Physiol 263: L645–L649, 1992
Stov K, Fenger-Gron, Mulvany MJ: Effects of angiotensin inhibitor, a calcium antagonist and an endothelin receptor antagonist on renal afferent arteriolar structure. Hypertension 28: 464–471, 1996
Becker RHA, Linz W, Scholkens BA: Pharmacological interference with the cardiac Renin-angiotensin system. J Cardiovasc Pharmacol 14: S10–S15, 1989
Geisterfer AAT, Peach MJ, Owens GK: Angiotensin II induces hypertrophy, not hyperplasia of cultured rat aortic smooth muscle cells. Circ Res 62: 749–756, 1988
Powell JS, Clozel J, Muller RKM, Kuhn H, Heffi F, Hosang M, Bawngartner HR: Inhibitors of ACE prevent myointimal proliferation after vascular injury. Science 245: 186–188, 1989
Zambetis Bellesis M, Dusting GJ, Mendelsohn FA, Richardson K: Autoradiographic localization of ACE and ang II binding sites in early atheroma like lesion in rabbit arteries. Clin Exp Pharmacol Physiol 18: 337–340, 1991
Asai K, Funald C, Hayashi T, Yamada K, Naito M, Kuzuya M, Yoshida F, Yoshimine N, Kuzuya F: Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol fed rabbits. Arteriosclerosis and Thrombosis 13: 892–899, 1993
Wright JW, Mizutani S, Murray CE, Amir HZ, Harding JW: Aminopeptidase induced elevations and reductions in blood pressure in the SHR. J Hypertens 8: 969–974, 1990
Umegaki K, Inoue Y, Tomita T: The appearance of “exhausted” platelets at the time of stroke in stroke prone SHR. Thromb Hemostasis 54: 764–767, 1985
Umegaki K, Saegusa H, Kurokawa M, Ichikawa T: Effects of vitamin E administration on platelet function and serum lipid peroxides in DOCA-Salt hypertensive rats. Thromb Hemostasis 65: 411–414, 1991
Szczepanski M, Staff-Ziehnska: Fibrinolytic activity in thrombin infused rabbits. Thrombosis Research 39: 127–131, 1985
Beller FK, Mitchell PS, Gorstein F: Fibrin deposition in the rabbit kidney produced by protease inhibitors. Thromb Diathes Haemorrh 17: 427–439, 1967
Comp PC, Jacocks RM, Ferrell GL, Esmon CT: Activation of protein C in vivo. J Clin Invest 70: 127–134, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rajashree, S., Puvanakrishnan, R. Dexamethasone induced alterations in the levels of proteases involved in blood pressure homeostasis and blood coagulation in rats. Mol Cell Biochem 197, 203–208 (1999). https://doi.org/10.1023/A:1006991009036
Issue Date:
DOI: https://doi.org/10.1023/A:1006991009036