R. Rauch et Ha. Schmid, Functional evidence for subfornical organ-intrinsic conversion of angiotensin I to angiotensin II, AM J P-REG, 45(6), 1999, pp. R1630-R1638
Citations number
46
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Using extracellular electrophysiological recording in an in vitro slice pre
paration, we investigated whether ANG I can be locally converted to the fun
ctionally active ANG II within the rat subfornical organ (SFO). ANG I and A
NG II (10(-8)-10(-7) M) excited similar to 75% of all neurons tested with b
oth peptides (n = 25); the remainder were insensitive. The increase in firi
ng rate and the duration and the latency of the responses of identical neur
ons, superfused with equimolar concentrations of ANG I and ANG II, were not
different. The threshold concentrations of the ANG I- and ANG II-induced e
xcitations were both 10(-9) M. Inhibition of the angiotensin-converting enz
yme by captopril (10(-4) M; n = 8) completely blocked the ANG I-induced exc
itation, a 10-fold lower dose was only effective in two of four neurons. Th
e AT(1)-receptor antagonist losartan (10(-5) M; n = 6) abolished the excita
tion caused by ANG I and ANG II. Subcutaneous injections of equimolar doses
of ANG I and ANG II (200 mu l; 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) s
uppressed the dipsogenic response of ANG I entirely (n = 11). These data pr
ovide direct functional evidence for an SFO-intrinsic renin-angiotensin sys
tem (RAS) and underline the importance of the SFO as a central nervous inte
rface connecting the peripheral with the central RAS.