EFFECTS OF INTRACEREBROVENTRICULAR INJECTIONS OF LOSARTAN OR PD123319ON ARTERIAL-PRESSURE AND HEART-RATE OF SODIUM REPLETE AND SODIUM DEPLETE RATS

Angiotensin II (Ang II) non-peptide antagonists were injected i.c.v. ( 6.25-200 nmol, n = 5-8 rats/group). In sodium replete rats, losartan ( AT(1) receptor antagonist) induced an increase in mean arterial pressu re (MAP) and in heart rate (HR) by 3rd ventricular (3rdV) injection, a nd an weaker presser response and bradycardia by 4th ventricular (4thV ) injection, PD123319 (AT(2) receptor antagonist) induced an increase in MAP acid in HR by 3rdV injection, and an increase in MAP and no alt eration in HR by 4thV injection. In sodium deplete (furosemide plus re moval of ambient sodium for 24 h) rats, losartan induced an increase i n MAP and no alteration in HR by 3rdV injection, and no alteration in MAP and bradycardia by 4thV injection. PD123319 induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and bradycard ia by 4thV injection. Thus, there were no fall in MAP by central injec tions of Ang II antagonists. Intravenous injection of losartan, but no t of PD123319, induced a fall in MAP in both sodium replete and sodium deplete animals. Therefore, losartan and PD123319 can have similar ef fects on MAP and HR when injected intracerebroventricularly, although some differences are also present. The bradycardia is consistent with an withdrawal of Ang II inhibitory action on baroreflex.