Intravenous losartan inhibits the increase in plasma luteinizing hormone and water intake produced by intraventricular angiotensin II.
In the presence of sex hormones, intraventricular injection of angiotensin II in female rats increases luteinizing hormone (LH) secretion, and this response is blocked by intraventricular losartan. There is evidence that in doses of 3 mg/kg or more systemically administered losartan blocks brain as well as peripheral AT1 angiotensin II receptors. Therefore, we tested the effect of intravenous losartan, 1 and 10 mg/kg, on the LH response to intraventricular angiotensin II in ovariectomized rats treated with estrogen and progesterone. The larger dose of losartan abolished the LH response. It also produced a marked reduction in the drinking response to intraventricular angiotensin II. The data provide additional evidence that in larger doses, peripherally administered losartan can penetrate the brain, and support the hypothesis that in female rats, the brain renin-angiotensin system plays an excitatory role in the regulation of LH secretion.
Palmer
A A
AA
Department of Physiology, University of California, San Francisco 94143-0444.
Steele
M K
MK
Shackelford
R L
RL
Ganong
W F
WF
D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects*; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D019808:Losartan; D007986:Luteinizing Hormone / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D007986:Luteinizing Hormone; D019808:Losartan