AREGU June 45/6

Rauch, Matthias, and Herbert A. Schmid. Functional evidence for subfornical organ-intrinsic conversion of angiotensin I to angiotensin II. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R1630–R1638, 1999.—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 (1028–1027 M) excited ,75% of all neurons tested with both peptides (n 5 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 Iand ANG II-induced excitations were both 1029 M. Inhibition of the angiotensin-converting enzyme by captopril (1024 M; n 5 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 (1025 M; n 5 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 3 1024 M) in water-sated rats similarly increased water intake by 2.4 6 0.5 (n 5 16) and 2.7 6 0.4 ml (n 5 20) after 1 h, respectively. Control rats receiving saline drank 0.07 6 0.06 ml under these conditions. Pretreatment with a low dose of captopril (2.3 3 1023 M) 10 min before the injection of ANG I caused a water intake of 2.8 6 0.5 ml (n 5 10), whereas a high dose of captopril (4.6 3 1021 M) suppressed the dipsogenic response of ANG I entirely (n 5 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.