Differential Regulation of Protective and Harmful Renin Transcripts by the cAMP/PKA/Ca²⁺-Pathway in Cardiac H9c2...

Two different renin isoforms are expressed in extrarenal tissues. The classical renin-a has been associated with detrimental effects, whereas renin-b exerts protective effects during glucose starvation. Glucose starvation selectively increased renin-b mRNA levels. 8Br-cAMP increased renin-a mRNA levels independently of glucose as well as of renin-b in glucose-starved cells. Adenylyl cyclase (AC) stimulation by forskolin increased expression of both renin transcripts, while AC inhibition by SQ22536 produced the opposite effect. PKA inhibition by KT5720 reduced the mRNA levels of both renin transcripts glucose-independently. Forskolin reversed the effect of KT5720 on renin mRNA levels. A23187-mediated increase in [Ca²⁺]i increased renin-b mRNA levels in glucose-starved cells. Ca²⁺ chelator BAPTA decreased renin-a mRNA expression in control cells and renin-b levels glucose-independently. Forskolin reversed the BAPTA-mediated decreases in renin-a but not renin-b expression. While the regulation of renin transcript levels by cAMP and PKA resembled known regulation in the kidney, the effect of intracellular free Ca²⁺ levels were opposite. This supports the existence of a separate renin system in cardiac cells.