Background: 

The enzymatic effect of renin is to generate angiotensin I from angiotensinogen. Nonenzymatic effects of renin include an increase of cell lengths of cardiomyocytes. Therefore, renin via its nonenzymatic effects is unique among other pro-hypertrophic agonists that increase cell widths but not cell lengths. Hyperglycaemia improves the nonenzymatic effects of renin on cardiomyocytes. Rosiglitazone, a PPARg activator reduces the survival of diabetic post myocardial infarct patients. Therefore, we hypothesized that PPARg may interfere with nonenzymatic renin effects.

Methods: 

Isolated cardiomyocytes from normotensive rats and those overexpressing renin as well as from mice with a cardiac restricted knockout of PPARg were isolated and the cell lengths and cross sectional areas were determined. Rats were feeded with rosiglitazone for 7 days at the age of 4 months. Captopril was used as a control drug to lower blood pressure in a similar way than with pioglitazone.

Results: 

in vitro, renin induces an increase in cardiomyocytes cell lengths by 9.4% (96.58 mm vs. 88.30 mm, n=447 cells). GW1929, a PPARg activator attenuated this renin effect (+2.7%, 90.68 mm). Isolated myocytes from PPARg knockout mice were longer than those from the nontransgenic littermates (4.3%). Myocytes isolated from renin overexpressing rats were longer than those of the non-transgenic littermates (12.3%; 136.97 mm vs. 121.94 mm), n=43 cells). Feeding these rats with pioglitazone, but not with captopril, reduced this increase in cell lengths. In ex vivo perfused Langendorff hearts from these animals left ventricular developed pressure (86.3 mm Hg) was higher than in the non-transgenic controls (64.8 mm Hg, each 240 bpm).

Conclusion: 

These data identify renin as a main regulator of cell lengths in vivo and in vitro. The effect of renin is antagonized by PPARg activation. Hearts with an improved cell length had also improved heart function.