The ability of propranolol to inhibit the development of polyploidy in aortic vascular smooth muscle cells associated with hypertension was studied in deoxycorticosterone (DOC)-salt treated rats. Six-week treatment with DOC-salt resulted in significant increases in systolic blood pressure, heart weight, and aortic weight in treated animals compared to increases in uninephrectomized controls. Additionally, the percentage of tetraploid nuclei in aortic smooth muscle cells increased to 17.0 +/- 0.2% in DOC-salt treated rats versus 7.8 +/- 0.3% in normotensive controls. Administration of propranolol (500 mg/L in drinking water) did not inhibit the development of hypertension for up to 4 weeks or the associated increase in cardiac or aortic weight in DOC-salt-treated rats, but did prevent the increase in polyploidy of aortic smooth muscle cell nuclei (8.9 +/- 0.9% in propranolol-treated rats compared to 7.8 +/- 0.3% in normotensive controls). These results indicate that propranolol inhibits the development of hypertension-induced polyploidy in aortic smooth muscle cells of DOC-salt-treated rats and that factors other than blood pressure may be important in this change.