Effects of losartan on bladder dysfunction due to aging-related severe hypertension in rats

• Published in: European journal of pharmacology 2022-05, Vol.922, p.174911-174911, Article 174911
• Main Authors: Shimizu, Shogo, Nagao, Yoshiki, Kurabayashi, Atsushi, Shimizu, Takahiro, Higashi, Youichirou, Karashima, Takashi, Saito, Motoaki
• Format: Article
• Language: English
• Subjects: Aging; Angiotensin II type 1 receptor blocker; Angiotensin Receptor Antagonists - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Bladder dysfunction; Blood Pressure; Body Weight; Hypertension; Hypertension - complications; Hypertension - drug therapy; Kidney Diseases; Losartan - pharmacology; Losartan - therapeutic use; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Spontaneously hypertensive rat; Urinary Bladder
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2022.174911

Aging is a major risk factor for bladder dysfunction. Anti-hypertensive drugs, angiotensin II type 1 receptor blockers (ARBs), are reported to ameliorate lower urinary tract dysfunction in rodent models and humans. We aimed to examine the preventive effect of an ARB, losartan, against bladder dysfunction due to aging-related severe hypertension. Male spontaneously hypertensive rats (SHRs) (36-week-old) were administered losartan (0, 3, or 10 mg/kg, p.o.) for 18 weeks. Age-matched, vehicle-treated Wistar Kyoto rats (WKYs) were used as controls. After the treatments, bladder and renal weight, mean blood pressure, and voiding parameters were measured. Additionally, detrusor thickness and bladder arterial wall thickness were evaluated using hematoxylin and eosin staining. Renal morphology was also assessed using periodic acid-Schiff staining. Compared to WKYs, SHRs demonstrated significantly higher bladder weight/body weight ratio (BBR), renal weight/body weight ratio, mean blood pressure, detrusor thickness, bladder arterial wall thickness, urine output, water intake, post-voiding residual urine volume, bladder capacity, intercontraction interval, and rate of glomerular and tubular injury and a lower urine osmolality. A low dose of losartan decreased the urine output, post-voiding residual urine volume, and bladder capacity in SHRs but not mean blood pressure in SHRs. A high dose of losartan decreased the BBR, mean blood pressure, detrusor thickness, bladder arterial wall thickness, post-voiding residual urine volume, bladder capacity, intercontraction interval, and glomerular and tubular injury in SHRs. Losartan inhibits bladder dysfunction in aged SHRs. The ARB losartan might be a preventive drug for bladder dysfunction due to aging-related severe hypertension. [Display omitted] •Losartan decreased blood pressure in spontaneously hypertensive rats (SHRs).•Losartan decreased bladder weight and bladder arterial wall thickness in SHRs.•Losartan ameliorated bladder dysfunction and polyuria in SHRs.•Losartan decreased glomerular and tubular injury in SHRs.•Losartan therapy might prevent hypertension-related bladder dysfunction.