Published Online
on February 17, 2003

A more recent version of this article appeared on March 1, 2003

This Article Full Text (PDF) All Versions of this Article: 41/3/576    most recent 01.HYP.0000058002.67558.6Ev1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Collister, J. P. Articles by Hendel, M. D. Search for Related Content PubMed PubMed Citation Articles by Collister, J. P. Articles by Hendel, M. D. Related Collections Cardiovascular Pharmacology ACE/Angiotension receptors Autonomic, reflex, and neurohumoral control of circulation

Submitted on October 29, 2002
Revised on November 20, 2002

Role of the Subfornical Organ in the Chronic Hypotensive Response to Losartan in Normal Rats

John P. Collister^* and Michael D. Hendel

From the Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St Paul.

^* To whom correspondence should be addressed. E-mail: colli066{at}tc.umn.edu.

Abstract--Angiotensin II is known to act at a unique set of brain regions known as the circumventricular organs. These structures lack the normal blood-brain barrier and are therefore thought to participate in the central nervous system processing of neuroendocrine signals. We have reported that chronic treatment with the angiotensin type 1 (AT₁) receptor antagonist, losartan, decreases arterial pressure in normotensive rats. Furthermore, this hypotension is attenuated in area postrema-lesioned rats, suggesting a role of endogenous angiotensin II at this circumventricular organ. Another circumventricular organ, the subfornical organ (SFO), has also been shown to mediate actions of angiotensin II. The present study tested the hypothesis that the SFO is a central site of action of endogenous angiotensin II at AT₁ receptors. Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus, and the SFO was sham or electrolytically lesioned. One week later, rats were instrumented with venous catheters and radiotelemetry pressure transducers for continuous infusion and monitoring of mean arterial pressure, respectively. After 3 days of control, losartan was administered intravenously (10 mg · kg^-1 · d^-1) for 10 days in both SFO-lesioned and sham rats. By day 4 of losartan administration, mean arterial pressure had decreased to 75±2 mm Hg in sham rats (n=9) but had only fallen to 83±2 mm Hg in lesioned rats (n=10). This attenuated hypotensive response in SFO-lesioned rats continued through day 10 of losartan treatment. These results support the hypothesis that the SFO mediates part of the hypotensive effects of chronic AT₁ receptor blockade in the normotensive rat.

Key words: antagonists, angiotensin • autonomic nervous system • blood pressure • brain • receptors, angiotensin II • renin-angiotensin system • circumventricular organ

This article has been cited by other articles:

				M. Maliszewska-Scislo, H. Chen, R. A. Augustyniak, D. Seth, and N. F. Rossi Subfornical organ differentially modulates baroreflex function in normotensive and two-kidney, one-clip hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R741 - R750. [Abstract] [Full Text] [PDF]

				J. P Collister and D. B Nahey Changing dietary sodium alters the chronic cardiovascular effects of losartan in rats Journal of Renin-Angiotensin-Aldosterone System, March 1, 2008; 9(1): 10 - 16. [Abstract] [PDF]

				D. B. Nahey and J. P. Collister ANG II-induced hypertension and the role of the area postrema during normal and increased dietary salt Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H694 - H700. [Abstract] [Full Text] [PDF]

				M. D. Hendel and J. P. Collister Sodium balance, arterial pressure, and the role of the subfornical organ during chronic changes in dietary salt Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H426 - H431. [Abstract] [Full Text] [PDF]

				J. W. Osborn, F. Jacob, and P. Guzman A neural set point for the long-term control of arterial pressure: beyond the arterial baroreceptor reflex Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2005; 288(4): R846 - R855. [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]

				J. Grobe, N. Rowland, and M. Katovich ROLE OF ANGIOTENSIN II AND THE SUBFORNICAL ORGAN IN THE PHARMACOLOGICAL ACTIONS OF ETHANOL Alcohol Alcohol., September 1, 2004; 39(5): 410 - 417. [Abstract] [Full Text] [PDF]

				J. P Collister and M. D Hendel The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 176 - 179. [Abstract] [PDF]