1. Functional evidence for subfornical organ-intrinsic conversion of angiotensin I to angiotensin II.
- Author
-
Rauch M and Schmid HA
- Subjects
- Angiotensin I antagonists & inhibitors, Angiotensin I physiology, Angiotensin II antagonists & inhibitors, Angiotensin II physiology, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors pharmacology, Animals, Captopril pharmacology, Dose-Response Relationship, Drug, Drinking drug effects, Drinking physiology, Electrophysiology, Losartan pharmacology, Male, Rats, Rats, Wistar, Reaction Time physiology, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Subfornical Organ drug effects, Subfornical Organ physiology, Angiotensin I metabolism, Angiotensin II metabolism, Subfornical Organ metabolism
- 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. more...
- Published
- 1999
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