Evidence for bradykinin as a stimulator of thirst.
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.
Cadnapaphornchai
Melissa A
MA
Department of Medicine, University of Colorado School of Medicine, Denver, CO 80262, USA.
Rogachev
Boris
B
Summer
Sandra N
SN
Chen
Yung-Chang
YC
Gera
Lajos
L
Stewart
John M
JM
Schrier
Robert W
RW
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology; D003404:Creatinine / Q000378:metabolism; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D008297:Male; D011141:Polyuria / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013894:Thirst / Q000187:drug effects / Q000502:physiology*; D014556:Urine; D014867:Water / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D014867:Water; D002216:Captopril; D003404:Creatinine; D001920:Bradykinin