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Dense core vesicle proteins IA‐2 and IA‐2beta ‐ novel regulators of renin secretion and circadian blood pressure rhythms
Author(s) -
Kim Soo Mi,
Hirai Hiroki,
Cai Tao,
Chen Limeng,
FaulhaberWalter Robert,
Huang Yuning,
Mizel Diane,
Briggs Josie P,
Notkins Abner L,
Schnermann Jurgen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1250-a
Subject(s) - medicine , endocrinology , plasma renin activity , renin–angiotensin system , chemistry , circadian rhythm , aldosterone , blood pressure , biology
The dense core vesicle proteins IA‐2 and IA‐2β have recently been found in renal afferent arterioles in a location consistent with expression in juxtaglomerular cells. To identify a possible role of IAs in renin secretion we compared plasma renin concentration (PRC, ng AngI/ml hr) as index of renin release in wild type (WT) and IA‐2/IA‐2β double knockout mice (DKO; Kubosaki A. et al. 2005). PRC was lower in DKO than WT (596 ± 81 vs. 1454 ± 122; n=16 vs. n=10; p<.0001). Renin mRNA in DKO was 38.0 ± 5.8 % of WT (p<0.001, n=9). On a high NaCl diet (8%), PRC decreased in both genotypes remaining lower in DKO than WT (276 ± 59 vs. 676 ± 128; p<0.01). Furosemide increased PRC to a lesser extent in DKO than WT (to 5536 ± 620 vs. 9416 ± 956). GFR, plasma aldosterone, and urine osmolarity did not differ between DKO and WT. 24 h mean arterial blood pressure (MAP) measured by telemetry was not different in WT and DKO (106 ± 2 vs. 111 ± 3 mm Hg), but the day‐night difference in MAP (1.8 ± 1 mm Hg vs. 12 ± 1.4 mm Hg; p<.0001) or heart rate was abolished in DKO. Locomotor activity of DKO in the active phase was only 25.5% of WT. In summary: Basal renin synthesis and release is dependent upon IA‐2/IA‐2β, modulation of renin release by salt intake is maintained in IA DKO, and circadian MAP and locomotor variations are absent in IA DKO. We conclude: IAs are positive regulators of renin secretion, synthesis and circadian blood pressure and activity rhythms.