Area postrema lesion attenuates the long-term hypotensive effects of losartan in salt-replete rats.
We reported that the AT1 receptor antagonist losartan decreases arterial pressure in sodium-replete rats and that this response is attenuated in area postrema-lesioned (APx) rats (J. P. Collister, B. J. Hornfeldt, and J. W. Osborn. Hypertension 27: 598-606, 1996). In that study, food intake for the 3-wk period after sham lesion was restricted to that observed in APx rats. Food-restricted sham rats had lower arterial pressures and attenuated responses to losartan compared with control rats fed ad libitum. The present study examined whether these differences persisted months, rather than weeks after APx or sham lesions. Losartan was administered for 10 days to APx and two groups of sham rats 3 mo after APx or sham surgery. The first sham group was food restricted (SFR) for 3 wk after surgery, whereas the second sham group was allowed ad libitum (SAL) access to food. By day 8 of losartan administration, both sham groups demonstrated a marked hypotension (SFR: -38 +/- 4; SAL: -33 +/- 4 mmHg). This response was attenuated (P < 0.05) on the same day in APx rats (-17 +/- 3 mmHg). This trend continued throughout days 9 and 10. Because both sham groups responded similarly to losartan (yet significantly different from APx rats), these results demonstrate that transient decreases in food intake do not affect the response to losartan if rats are allowed an adequate recovery period. We conclude that the area postrema mediates part of the long-term hypotensive effects of AT1 receptor blockade in the conscious rat.
Collister
J P
JP
Department of Veterinary PathoBiology, University of Minnesota, St. Paul 55108, USA.
Osborn
J W
JW
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004326:Drinking; D005508:Food Deprivation; D006339:Heart Rate / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014882:Water-Electrolyte Balance
D000959:Antihypertensive Agents; D012982:Sodium, Dietary; D000804:Angiotensin II; D012083:Renin; D019808:Losartan