Involvement of central angiotensin II type 1 receptors in LPS-induced systemic vasopressin release and blood pressure regulation in rats.
The purpose of this study was to evaluate the involvement of central angiotensin II (ANG II) and ANG II type 1 (AT(1)) receptors in systemic release of arginine vasopressin (AVP) and blood pressure regulation during endotoxemia. LPS (150 microg/kg) was injected intravenously 30 min after intracerebroventricular (icv) losartan (50 microg), an AT(1) receptor antagonist, or subcutaneous (sc) captopril (50 mg/kg), an angiotensin-converting enzyme inhibitor. Rats with icv and sc saline injections served as control. LPS administration increased plasma AVP concentration from 2.1 +/- 0.2 to 15.2 +/- 2.5 pg/ml (60 min after LPS injection) without significant changes in plasma osmolality or hematocrit. LPS-induced AVP secretion was significantly attenuated by pretreatment with icv losartan (2.3 +/- 0.5 to 3.7 +/- 0.5 pg/ml) but was not attenuated after peripheral captopril treatment (2.2 +/- 0.6 to 17.6 +/- 4.2 pg/ml). LPS administration significantly decreased systolic blood pressure (SBP) by 22.7 +/- 5.4 mmHg after intravenous LPS injection in icv losartan-treated rats, while SBP remained unchanged in vehicle-treated or sc captopril-treated rats by intravenous LPS. These results indicate that central AT(1) receptors, not responsive to peripheral ANG II, play an important role in systemic AVP secretion and maintenance of blood pressure during endotoxemia.
Department of Environmental Health, Nara Women's Univesity, Kitauoya Nishimachi, Nara 630-8506, Japan.
Fumihiro
F
Shimizu
Toshihiro
T
Kasai
Akira
A
Takamata
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D008070:Lipopolysaccharides; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D001127:Arginine Vasopressin; D002216:Captopril; D019808:Losartan