Blockade of renin-angiotensin system prevents micturition dysfunction in renovascular hypertensive rats.

Autor: Ramos-Filho AC; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil., Moscoso JA; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil., Calmasini F; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil., Faria Jde A; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil., Anhê GF; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil., Mónica FZ; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil., Antunes E; Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil. Electronic address: edson.antunes@uol.com.br.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2014 Sep 05; Vol. 738, pp. 285-92. Date of Electronic Publication: 2014 May 29.
DOI: 10.1016/j.ejphar.2014.05.038
Abstrakt: 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.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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