title: Blockade of renin-angiotensin system prevents micturition dysfunction in renovascular hypertensive rats.
abstract: Association between hypertension and bladder symptoms has been described. We hypothesized that micturition dysfunction may be associated with renin-angiotensin system (RAS) acting in urethra. The effects of the anti-hypertensive drugs losartan (AT1 antagonist) and captopril (angiotensin-converting enzyme inhibitor) in comparison with atenolol (β1-adrenoceptor antagonist independently of RAS blockade) have been investigated in bladder and urethral dysfunctions during renovascular hypertension in rats. Two kidney-1 clip (2K-1C) rats were treated with losartan (30 mg/kg/day), captopril (50mg/kg/day) or atenolol (90 mg/kg/day) for eight weeks. Cystometric study, bladder and urethra smooth muscle reactivities, measurement of cAMP levels and p38 MAPK phosphorylation in urinary tract were determined. Losartan and captopril markedly reduced blood pressure in 2K-1C rats. The increases in non-voiding contractions, voiding frequency and bladder capacity in 2K-1C rats were prevented by treatments with both drugs. Likewise, losartan and captopril prevented the enhanced bladder contractions to electrical-field stimulation (EFS) and carbachol, along with the impaired relaxations to β-adrenergic-cAMP stimulation. Enhanced neurogenic contractions and impaired nitrergic relaxations were observed in urethra from 2K-1C rats. Angiotensin II also produced greater urethral contractions that were accompanied by higher phosphorylation of p38 MAPK in urethral tissues of 2K-1C rats. Losartan and captopril normalized the urethral dysfunctions in 2K-1C rats. In contrast, atenolol treatment largely reduced the blood pressure in 2K-1C rats but failed to affect the urinary tract smooth muscle dysfunction. The urinary tract smooth muscle dysfunction in 2K-1C rats takes place by local RAS activation irrespective of levels of arterial blood pressure.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil.
authors.forename: Antonio Celso S
authors.initials: AC
authors.lastname: Ramos-Filho
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil.
authors.forename: Julio Alejandro Rojas
authors.initials: JA
authors.lastname: Moscoso
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Calmasini
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil.
authors.forename: Juliana de Almeida
authors.initials: Jde A
authors.lastname: Faria
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil.
authors.forename: Gabriel Forato
authors.initials: GF
authors.lastname: Anhê
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil.
authors.forename: Fabíola Z
authors.initials: FZ
authors.lastname: Mónica
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil. Electronic address: edson.antunes@uol.com.br.
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014521:Urethra / Q000187:drug effects / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D000804:Angiotensin II; D001262:Atenolol; D002216:Captopril; D000242:Cyclic AMP; D019808:Losartan
keywords: 2K-1C; Captopril; Losartan; P38 MAPK; Urethra; cAMP