Effects of stretch, angiotensin II, and aldosterone on nonmyocyte hyperplasia

Heart disease is a common cause of death within the United States. Left ventricular hypertrophy is a risk factor for heart disease and may be induced by increased mechanical load due to increased blood pressure and humoral factors such as products of the renin angiotensin system. The hypertrophic response includes nonmyocyte hyperplasia and myocyte hypertrophy. Angiotensin II has been shown to induce nonmyocyte hyperplasia and increased protein synthesis within myocytes. Additionally, experiments have been performed which suggest that stretch induces hypertrophy in myocytes and hyperplasia in nonmyocytes.

This study examined the effect of stretch combined with products of the renin-angiotensin system on nonmyocyte hyperplasia. Cultured cardiac nonmyocytes were stretched at 10% for 24 hours while being treated with angiotensin II or aldosterone. Nonmyocyte hyperplasia was quantified using ³H-thymidine incorporation as a measure of DNA synthesis. Nonmyocytes treated with angiotensin II while being stretched exhibited a statistically significant increase in ³H-thymidine incorporation when compared to Although aldosterone treatment produced increased ³H-thymidine incorporation when compared to untreated cells, the effect was not statistically significant. unstretched angiotensin II treated nonmyocytes.

Experiments were then performed to examine if stretch increased renin mRNA synthesis, suggesting an upregulation of the renin-angiotensin system due to mechanical stimulus. Nonmyocytes were stretched at 10% for 48 hours. RNA was extracted and subjected to RT-PCR. PCR products were run on a 5% acrylamide gel for observation. Faint renin bands were seen, but there was not an apparent increase in renin mRNA in response to stretch.

These results suggest that nonmyocyte hyperplasia is increased by the combination of angiotensin II and stretch. From the PCR studies it was determined that autocrine production of angiotensin II utilizing renin is not probable. Other possibilities exist for a local renin-angiotensin system including a paracrine production of angiotensin II from myocytes to effect nonmyocyte hyperplasia or an autocrine production of angiotensin II within nonmyocytes utilizing an enzyme other than renin.