Endocrinology, Vol 118, 819-823, Copyright © 1986 by Endocrine Society

ARTICLES

Intracerebroventricular infusion of aldosterone induces hypertension in rats

EP Gomez-Sanchez

There is suggestive evidence for the direct participation of mineralocorticoids in the production of centrally mediated hypertension. Unilaterally nephrectomized Sprague-Dawley rats received a continuous infusion for 30 days using implanted osmotic minipumps with 1) artificial spinal fluid (CSF) intracerebroventricularly (icvt); 2) 0.005 micrograms aldosterone/h icvt; 3) 0.005 micrograms aldosterone/h sc; 4) 0.5 micrograms aldosterone/h sc. There was no significant difference between the groups in average weight gain (52 +/- 2 g) or organ weight to body weight, nor was urine volume increased above normal except in the group receiving the high sc dose of aldosterone. Blood pressure was significantly elevated only in those animals receiving 0.005 micrograms aldosterone/h icvt and 0.5 micrograms aldosterone/h sc. A second experiment was done using a specific spironolactone-type mineralocorticoid antagonist, prorenone. The rats were grouped as follows: 1) CSF icvt; 2) 0.005 micrograms/h aldosterone icvt; 3) 0.005 micrograms/h aldosterone plus 0.005 micrograms/h prorenone icvt; 4) 0.005 micrograms/h aldosterone plus 0.02 micrograms/h prorenone icvt; 5) 0.02 micrograms/h prorenone icvt. This study confirmed that this minute dose of aldosterone infused icvt produced a statistically significant increase in blood pressure with no increase in urine volume. Both the low, 0.005 micrograms/h, and high, 0.02 micrograms/h, doses of prorenone antagonized the pressor effect of aldosterone when infused with aldosterone into the lateral cerebral ventricle. The groups receiving 0.02 micrograms/h prorenone icvt or CSF icvt did not differ significantly in those parameters measured. A dose of aldosterone that was too small to produce changes in blood pressure when infused systemically was found to produce hypertension without polydypsia/polyuria when infused intrathecally. This pressor effect could be blocked by the concomitant infusion of a specific antagonist, prorenone. The study presented offers strong circumstantial evidence supporting a direct hypertensinogenic effect of aldosterone within the central nervous system.

This article has been cited by other articles:

				T. Matsukawa and T. Miyamoto Does infusion of ANG II increase muscle sympathetic nerve activity in patients with primary aldosteronism? Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1873 - R1879. [Abstract] [Full Text] [PDF]

				D. G. Romero, M. W. Plonczynski, C. A. Carvajal, E. P. Gomez-Sanchez, and C. E. Gomez-Sanchez Microribonucleic Acid-21 Increases Aldosterone Secretion and Proliferation in H295R Human Adrenocortical Cells Endocrinology, May 1, 2008; 149(5): 2477 - 2483. [Abstract] [Full Text] [PDF]

				J. M. C. Connell, S. M. MacKenzie, E. M. Freel, R. Fraser, and E. Davies A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function Endocr. Rev., April 1, 2008; 29(2): 133 - 154. [Abstract] [Full Text] [PDF]

				P. Ye, C. J Kenyon, S. M MacKenzie, K. Nichol, J. R Seckl, R. Fraser, J. M C Connell, and E. Davies Effects of ACTH, dexamethasone, and adrenalectomy on 11{beta}-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system J. Endocrinol., February 1, 2008; 196(2): 305 - 311. [Abstract] [Full Text] [PDF]

				S. M MacKenzie, D. Dewar, W. Stewart, R. Fraser, J. M C Connell, and E. Davies The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue J. Endocrinol., January 1, 2008; 196(1): 123 - 130. [Abstract] [Full Text] [PDF]

				D. G. Romero, M. W. Plonczynski, B. L. Welsh, C. E. Gomez-Sanchez, M. Y. Zhou, and E. P. Gomez-Sanchez Gene expression profile in rat adrenal zona glomerulosa cells stimulated with aldosterone secretagogues Physiol Genomics, December 19, 2007; 32(1): 117 - 127. [Abstract] [Full Text] [PDF]

				H. J. Adrogue and N. E. Madias Sodium and Potassium in the Pathogenesis of Hypertension N. Engl. J. Med., May 10, 2007; 356(19): 1966 - 1978. [Full Text] [PDF]

				J. C. Geerling, W. C. Engeland, M. Kawata, and A. D. Loewy Aldosterone Target Neurons in the Nucleus Tractus Solitarius Drive Sodium Appetite J. Neurosci., January 11, 2006; 26(2): 411 - 417. [Abstract] [Full Text] [PDF]

				J. M C Connell and E. Davies The new biology of aldosterone J. Endocrinol., July 1, 2005; 186(1): 1 - 20. [Abstract] [Full Text] [PDF]

				B. S. Huang and F. H. H. Leenen Blockade of brain mineralocorticoid receptors or Na+ channels prevents sympathetic hyperactivity and improves cardiac function in rats post-MI Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2491 - H2497. [Abstract] [Full Text] [PDF]

				E. P. Gomez-Sanchez, J. Samuel, G. Vergara, and N. Ahmad Effect of 3{beta}-hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt-sensitive rat Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R389 - R393. [Abstract] [Full Text] [PDF]

				B. S. Huang, H. Wang, and F. H. H. Leenen Chronic central infusion of aldosterone leads to sympathetic hyperreactivity and hypertension in Dahl S but not Dahl R rats Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H517 - H524. [Abstract] [Full Text] [PDF]

				M. D. Hendel and J. P. Collister Contribution of the subfornical organ to angiotensin II-induced hypertension Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H680 - H685. [Abstract] [Full Text] [PDF]

				M. C. HOLMES, J. L.W. YAU, Y. KOTELEVTSEV, J. J. MULLINS, and J. R. SECKL 11{beta}-Hydroxysteroid Dehydrogenases in the Brain: Two Enzymes Two Roles Ann. N.Y. Acad. Sci., December 1, 2003; 1007(1): 357 - 366. [Abstract] [Full Text] [PDF]

				H. Wang, B. S. Huang, and F. H. H. Leenen Brain sodium channels and ouabainlike compounds mediate central aldosterone-induced hypertension Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2516 - H2523. [Abstract] [Full Text] [PDF]

				T. H. Hostetter and H. N. Ibrahim Aldosterone in Chronic Kidney and Cardiac Disease J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2395 - 2401. [Abstract] [Full Text] [PDF]

				P. Ye, C. J. Kenyon, S. M. MacKenzie, J. R. Seckl, R. Fraser, J. M. C. Connell, and E. Davies Regulation of Aldosterone Synthase Gene Expression in the Rat Adrenal Gland and Central Nervous System by Sodium and Angiotensin II Endocrinology, August 1, 2003; 144(8): 3321 - 3328. [Abstract] [Full Text] [PDF]

				W. Qin, A. E. Rudolph, B. R. Bond, R. Rocha, E. A.G. Blomme, J. J. Goellner, J. W. Funder, and E. G. McMahon Transgenic Model of Aldosterone-Driven Cardiac Hypertrophy and Heart Failure Circ. Res., July 11, 2003; 93(1): 69 - 76. [Abstract] [Full Text] [PDF]

				C. Ngarmukos and R. J. Grekin Nontraditional aspects of aldosterone physiology Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1122 - E1127. [Abstract] [Full Text] [PDF]

				W Shamim, M Yousufuddin, D P Francis, P Gualdiero, J W Honour, S D Anker, and A J S Coats Raised urinary glucocorticoid and adrenal androgen precursors in the urine of young hypertensive patients: possible evidence for partial glucocorticoid resistance Heart, August 1, 2001; 86(2): 139 - 144. [Abstract] [Full Text] [PDF]

				S. H.M. van Uum, A. R.M.M. Hermus, P. Smits, T. Thien, and J. W.M. Lenders The role of 11{beta}-hydroxysteroid dehydrogenase in the pathogenesis of hypertension Cardiovasc Res, April 1, 1998; 38(1): 16 - 24. [Abstract] [Full Text] [PDF]

				R. Rocha, P. N. Chander, K. Khanna, A. Zuckerman, and C. T. Stier Jr. Mineralocorticoid Blockade Reduces Vascular Injury in Stroke-Prone Hypertensive Rats Hypertension, January 1, 1998; 31(1): 451 - 458. [Abstract] [Full Text] [PDF]

				H. M. Kubisch, S. Mathialagan, and E. P. Gomez-Sanchez Modulation of Blood Pressure in the Dahl SS/jr Rat by Embryo Transfer Hypertension, January 1, 1998; 31(1): 540 - 545. [Abstract] [Full Text] [PDF]

				Y. Takeda, I. Miyamori, T. Yoneda, K. Furukawa, S. Inaba, R. Takeda, and H. Mabuchi Brain Nitric Oxide Synthase Messenger RNA in Central Mineralocorticoid Hypertension Hypertension, October 1, 1997; 30(4): 953 - 956. [Abstract] [Full Text]

				M. A. Magiakou, G. Mastorakos, K. Zachman, and G. P. Chrousos Blood Pressure in Children and Adolescents with Cushing's Syndrome before and after Surgical Cure J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1734 - 1738. [Abstract] [Full Text] [PDF]