title: Functional evidence for subfornical organ-intrinsic conversion of angiotensin I to angiotensin II.
abstract: Using extracellular electrophysiological recording in an in vitro slice preparation, we investigated whether ANG I can be locally converted to the functionally active ANG II within the rat subfornical organ (SFO). ANG I and ANG II (10(-8)-10(-7) M) excited approximately 75% of all neurons tested with both peptides (n = 25); the remainder were insensitive. The increase in firing rate and the duration and the latency of the responses of identical neurons, superfused with equimolar concentrations of ANG I and ANG II, were not different. The threshold concentrations of the ANG I- and ANG II-induced excitations were both 10(-9) M. Inhibition of the angiotensin-converting enzyme by captopril (10(-4) M; n = 8) completely blocked the ANG I-induced excitation, a 10-fold lower dose was only effective in two of four neurons. The AT1-receptor antagonist losartan (10(-5) M; n = 6) abolished the excitation caused by ANG I and ANG II. Subcutaneous injections of equimolar doses of ANG I and ANG II (200 microliters; 2 x 10(-4) M) in water-sated rats similarly increased water intake by 2.4 +/- 0.5 (n = 16) and 2. 7 +/- 0.4 ml (n = 20) after 1 h, respectively. Control rats receiving saline drank 0.07 +/- 0.06 ml under these conditions. Pretreatment with a low dose of captopril (2.3 x 10(-3) M) 10 min before the injection of ANG I caused a water intake of 2.8 +/- 0.5 ml (n = 10), whereas a high dose of captopril (4.6 x 10(-1) M) suppressed the dipsogenic response of ANG I entirely (n = 11). These data provide direct functional evidence for an SFO-intrinsic renin-angiotensin system (RAS) and underline the importance of the SFO as a central nervous interface connecting the peripheral with the central RAS.
authors.affiliation: Max-Planck-Institut für Physiologische und Klinische Forschung, W. G. Kerckhoff-Institut, 61231 Bad Nauheim, Germany. m.rauch@kerckhoff.mpg.de
authors.forename: M
authors.initials: M
authors.lastname: Rauch
authors.forename: H A
authors.initials: HA
authors.lastname: Schmid
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D019808:Losartan