ANGIOTENSIN-II RESPONSIVENESS OF RAT PARAVENTRICULAR AND SUBFORNICAL ORGAN NEURONS IN-VITRO

The responsiveness of neurons in the hypothalamic paraventricular nucl eus to angiotensin II was investigated using extracellular single unit recording techniques in rat brain slices. Bath application of angiote nsin II at a concentration of 3 x 10(-7) M for 2 5 min resulted in exc itatory responses in 50.4% of 141 paraventricular cells tested. The me an increase in firing rate was 2.12 +/- 0.20 (mean +/- S.E.M.) spikes/ s, which represents a mean increase in activity of 149.8 +/- 16.5%. An giotensin II-sensitive neurons usually displayed irregular, phasic, or very slow spontaneous activity, with the majority of these neurons lo cated in the magnocellular region. Under physiological blockade of syn aptic transmission with low Ca2+/high Mg2+ medium, neuronal responses to this peptide remained in 12 (92.3%) of 13 cells tested. Application of three successive doses of angiotensin II ranging from 3 x 10(-9)-3 x 10(-7) M showed that neuronal responses were dose-dependent with an estimated threshold of 10(-8) M. In comparison with angiotensin III, angiotensin II not only stimulated more paraventricular cells, but usu ally induced larger excitatory responses. Angiotensin II subtype 1 rec eptor antagonist losartan completely blocked angiotensin II responsive ness in each of 14 paraventricular cells tested whereas PD 123319, an angiotensin II subtype 2 receptor antagonist, exhibited a partial inhi bitory effect in about one half of another 13 cells. In addition, sing le unit in vitro subfornical organ recordings demonstrate that angiote nsin II evokes greater excitatory responses than in the paraventricula r nucleus and that these effects are abolished by losartan application . These results support the hypothesis that within both the paraventri cular nucleus and subfornical organ angiotensin II is a bioactive pept ide which modulates neuronal activity and thus may exert significant c ontrol over neuroendocrine and autonomic functions.