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Protein kinase C signaling contributes to androgen amplification of angiotensin II‐induced renal vasoconstriction.
Author(s) -
Martin Doug,
Kost Curtis K,
Eyster Kathleen,
Song Jin
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.a1419-a
Subject(s) - endocrinology , medicine , protein kinase c , chelerythrine , androgen , angiotensin ii , vasoconstriction , kidney , castration , blood pressure , biology , signal transduction , hormone , microbiology and biotechnology
Androgens exacerbate hypertension development. Previously we showed that androgens increased pressor and renal responses to angiotensin II (Ang II). Protein kinase C (PKC) is a major signaling mechanism activated by Ang II. We tested the hypothesis that PKC contributes to androgen amplification of AII renal vascular responses. Five week old male New Zealand genetically hypertensive (NZGH) rats underwent sham operation, castration, or castration with testosterone replacement. At 16–17 weeks of age, rats were anesthetized and fitted with arterial and venous catheters and a renal artery flow probe. Mean arterial pressure (MAP) and renal vascular resistance (RVR) responses to Ang II infusion (20–80 ng/kg/min) were obtained before and after treatment with a PKC inhibitor (chelerythrine 80 ug/kg/min). Expression of PKC isoforms and CPI‐17, a downstream target of PKC, was assessed by RT‐PCR and/or Western blot. Both the MAP and RVR responses to Ang II were significantly exaggerated in androgen‐replete groups compared with the castrated group. Chelerythrine treatment significantly attenuated these differences. Expression of PKC delta mRNA and of CPI‐17 protein in the kidney was reduced by castration but restored with testosterone replacement. Collectively, these data suggest that androgen amplification of Ang II‐induced renal constrictor responses involves changes in PKC signaling mechanisms. These changes may contribute to androgen‐induced facilitation of hypertension development. Supported by NIH #63053, #69886, #74852 and INBRE 2P20RR016479 and AHA #0515443Z.