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 (10⁸-10⁷ M) excited ~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 10⁹ M. Inhibition of the angiotensin-converting enzyme by captopril (10⁴ 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 (10⁵ 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 µl; 2 × 10⁴ 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 × 10³ 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 × 10¹ 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.

captopril; losartan; thirst; drinking; osmoregulation; electrophysiology; renin-angiotensin system

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