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Am J Physiol Renal Physiol 286: F875-F880, 2004. First published January 6, 2004; doi:10.1152/ajprenal.00243.2003
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Evidence for bradykinin as a stimulator of thirst

Melissa A. Cadnapaphornchai,1,2 Boris Rogachev,1 Sandra N. Summer,1 Yung-Chang Chen,1,3 Lajos Gera,4 John M. Stewart,4 and Robert W. Schrier1

Departments of 1Medicine, 2Pediatrics, and 4Biochemistry, University of Colorado School of Medicine, Denver, Colorado 80262; and 3Division of Critical Care Nephrology, Chang Gung Memorial Hospital, Taipei, Taiwan

Submitted 14 July 2003 ; accepted in final form 2 January 2004

Angiotensin-converting enzyme inhibition (ACEI) with captopril has been shown to increase water intake and urine output in rats, but the mechanism is unknown. ACEI impairs the conversion of ANG I to ANG II, a dipsogenic hormone, and impairs the degradation of bradykinin. The goal of this study was to examine the role of bradykinin in the polydipsia and polyuria associated with ACEI. Male Sprague-Dawley rats received captopril (CPT; 20 mg·kg-1·day-1) in ground chow for 48 h. Water intake, food intake, and urine output were monitored and compared with control rats (CTL), rats receiving captopril treatment with limited water intake (CPT-LIM), and rats receiving captopril treatment with ad libitum water intake plus 24-h treatment with the bradykinin antagonist B-9430 (CPT-BK1). CPT rats consumed significantly more water and produced more urine vs. CTL. Urine osmolality was significantly decreased in CPT rats vs. CTL. Inner medullary aquaporin-2 (AQP2) protein abundance was also markedly decreased in CPT rats vs. CTL. These findings were reversed in CPT-LIM rats, suggesting captopril-induced primary polydipsia. CPT-BKI rats demonstrated parameters no different from CTL despite ad libitum water intake. Mean arterial pressure and 24-h creatinine clearance did not differ among groups. We conclude that ACEI with captopril induces primary polydipsia despite impaired production of the dipsogen ANG II and that this primary increase in water intake is likely the cause of the decreased protein abundance of inner medullary AQP2. Furthermore, this dipsogenic effect was reversed by antagonism of bradykinin, thus implicating this hormone in thirst regulation in the rat.

angiotensin-converting enzyme inhibition; aquaporin



Address for reprint requests and other correspondence: R. W. Schrier, Univ. of Colorado School of Medicine, 4200 E. Ninth Ave., Box C293, Denver, CO 80262 (E-mail: Robert.Schrier{at}UCHSC.edu).




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[Abstract] [Full Text] [PDF]




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