The hypothesis that endogenous angiotensin II (AII) acts at the area postrema (AP) to increase lumbar sympathetic nerve activity (LSNA) and heart rate (HR) over the entire baroreflex range of arterial pressure (BP) was tested in conscious rats. Three groups of male rats, AP lesioned (APX, n=8), sham with food restriction (SFR, n=7), and sham with food ad libitum (SAL, n=8) were placed on sodium deficient diet for 2-3 weeks to increase endogenous AII levels. Rats were instrumented with a nerve electrode and catheterized for BP measurement and drug delivery. One to two days later, baroreflex curves were generated by changing BP with nitroprusside and phenylephrine, before and 40 min after injection of losartan (LOS; 10 mg/kg, iv), the AII type 1 receptor antagonist. Post-LOS hypotension was prevented by methoxamine infusion. LOS produced similar decreases in LSNA from 100±0 to 63±3, 56±7, and 64±5 %, in the APX, SFR and SAL groups, respectively (all p<0.01). In all groups, LOS similarly shifted (p<0.01) the LSNA/BP curve to a lower BP (APX:101±3 to 87±3 mmHg; SFR:100±3 to 86±5 mmHg; SAL:97±3 to 85±3 mmHg), without affecting maximal gain. LOS decreased (p<0.01) maximum reflex LSNA in SFR (240±13 to 205±15%) and SAL (231±21 to 197±26%), but not in APX rats (184±11 to 177±9%). LOS also shifted the HR/BP curve to a lower BP and decreased maximum HR (p<0.05) similarly in all groups. In conclusion, the AP is not necessary for endogenous AII to increase LSNA or HR at most BP levels in sodium deprived rats, but is required for AII to enhance LSNA reflex maximum.
|Original language||English (US)|
|State||Published - Dec 1 1997|