Behavior of the renal kallikrein in spontaneously hypertensive rats: Influence of sexual hormones and aldosterone-sensitive distal nephron ion channels

The renal kallikrein-kinin system (RKKS) has been related to blood pressure control and sodium and water balance. We have previously shown that female spontaneously hypertensive rats (SHR) have high urinary kallikrein activity (UKa) and lower blood pressure (BP) than males whereas ovariectomy stimul...

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Published in:	Peptides (New York, N.Y. : 1980) Vol. 160; p. 170925
Main Authors:	Azurmendi, Pablo Javier, Toro, Ayelén Rayen, Celía, Alejandro Fabián, Guevara, Darío, Solerno, Martín Rogelio, Di Ciano, Luis Alberto, Toledo, Jorge Eduardo, Ibarra, Fernando Raúl, Arrizurieta, Elvira Emilia, Oddo, Elisabet Mónica
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-02-2023
Subjects:	Aldosterone - metabolism Aldosterone receptor Animals Epithelial sodium channel Epithelial Sodium Channels - genetics Epithelial Sodium Channels - metabolism Female Gonadectomy Hypertension - metabolism Ion Channels - metabolism Kallikreins - genetics Kallikreins - metabolism Kidney - metabolism Male Nephrons - metabolism Rats Rats, Inbred SHR Receptors, Mineralocorticoid - metabolism Rectifying outward potassium channel Renal kallikrein Sodium - metabolism Renal kallikrein Aldosterone receptor Rectifying outward potassium channel Epithelial sodium channel Gonadectomy
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Summary:	The renal kallikrein-kinin system (RKKS) has been related to blood pressure control and sodium and water balance. We have previously shown that female spontaneously hypertensive rats (SHR) have high urinary kallikrein activity (UKa) and lower blood pressure (BP) than males whereas ovariectomy stimulates UKa and diminishes BP. We also showed that high K+ intake and prepuberal gonadectomy (Gx) diminish BP with a concomitant increase in UKa and plasma aldosterone levels. Since kallikrein co-localize in the same distal nephron segments of aldosterone effectors, we explored the effect of pharmacological blockage of aldosterone receptor, epithelial Na+ (ENaC) and the rectifying outer medulla K+ (ROMK) channels in different gonad contexts on the gene expression, renal tissue content and urine release of kallikrein. Klk1 gene expression was determined by real-time PCR and enzymatic activity of kallikrein by the amidolytic method. We found that the inhibition of the aldosterone receptor by spironolactone increases kallikrein renal tissue storage and decreases its urinary activity, especially in Gx rats. Moreover, ENaC blockade by benzamil increases the renal content of kallikrein without affecting synthesis or excretion, especially in females and Gx animals, while the inhibition of ROMK by glibenclamide increases the synthesis and renal content of kallikrein only in intact male animals. We concluded that RKKS regulation showed sexual dimorphism and seemed to be modulated by sex hormones throughout a process involving aldosterone and the aldosterone-sensitive ion channels.. [Display omitted] •In SHR, sex and prepuberal Gx differentially regulate urine electrolyte composition.•Sp, Bz and Gli selectively changed urine Na+ and/or K+ according to sex and Gx.•Aldosterone, ENaC and ROMK influence KKS showing a sexual dimorphism pattern.•The blood pressure also showed a sexual dimorphism that disappeared after Gx.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0196-9781 1873-5169
DOI:	10.1016/j.peptides.2022.170925