title: Effects of acute and subchronic AT1 receptor blockade on cardiovascular, hydromineral and neuroendocrine responses in female rats.
abstract: Female Wistar rats were ovariectomized (OVX) and separated into two groups that received either estradiol cypionate (EC, 40 μg/kg, sc; OVX-EC) or vehicle (corn oil, sc; OVX-oil) for 14 consecutive days. On the 7th day of treatment, a subset of animals from both the OVX-oil and OVX-EC groups was subjected to subchronic losartan (AT1 receptor antagonist) treatment (0.1g/L in drinking water; ~15 mg/kg/day) for 7 days. Other group of OVX-oil and OVX-EC rats was submitted to an acute losartan injection (100mg/kg, ip) on the 14th day of hormone replacement. In both protocols, the following parameters were measured: I) mean arterial pressure (MAP) and heart rate (HR); II) water and 0.3M saline intake; III) angiotensin II (ANG II), atrial natriuretic peptide (ANP), vasopressin (AVP) and oxytocin (OT) plasma concentrations; and IV) urinary and plasma sodium concentrations. Acute AT1 blockade induced a significant reduction in the MAP in the OVX rats, resulting in increased HR and water intake, which were attenuated by estradiol therapy. Acute AT1 blockade also increased ANG II and OT and reduced ANP plasma concentrations, with no changes in AVP secretion. In addition, acute hypotension was accompanied by a decrease in natriuresis, which was unaltered by estradiol. Subchronic AT1 blockade induced a significant decrease in MAP without changing HR in both groups. Additionally, subchronic losartan treatment induced sodium appetite in OVX rats. Prolonged AT1 blockade increased ANG II and AVP and reduced ANP plasma concentrations. Moreover, it increased natriuresis but did not alter plasma OT concentrations. Finally, estradiol treatment attenuated the increase in salt intake and plasma ANG II concentrations induced by subchronic AT1 blockade. In conclusion, our results suggest differential adaptive responses to the acute or subchronic losartan treatment in OVX and OVX-EC rats.
authors: Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, BR 465 Km 07, CEP 23897970 Seropédica, Rio de Janeiro, Brazil. Electronic address: igaraujo@ufrrj.br.
authors: Iracema Gomes
authors: IG
authors: Araujo
authors: Lucila Leico Kagohara
authors: LL
authors: Elias
authors: José
authors: J
authors: Antunes-Rodrigues
authors: Luís Carlos
authors: LC
authors: Reis
authors: Andre Souza
authors: AS
authors: Mecawi
mesh_terms: D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D009320:Atrial Natriuretic Factor / Q000097:blood; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology*; D010052:Ovariectomy; D010121:Oxytocin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D014667:Vasopressins / Q000097:blood
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D014667:Vasopressins; D000804:Angiotensin II; D004958:Estradiol; D010121:Oxytocin; C007630:estradiol 17 beta-cypionate; D009320:Atrial Natriuretic Factor; D012964:Sodium; D019808:Losartan
keywords: AT1 receptors; Estrogen; Hypotension; Sodium appetite; Thirst