Digitalis Attenuates Arterial Hypertrophy in Experimental Hypertension

Abstract

Abstract

Several investigators have reported that digitalis administration reduces cardiac hypertrophy in rats with experimental hypertension. To determine whether digitalis similarly affects growth of arteries, we studied young (5- to 14-week-old), male, one-kidney, one-clip hypertensive rats (1K1C; n = 14) and one-kidney normotensive control rats (1K; n = 26). Half of the rats received digoxin (150 mg/kg body wt/day) in chow starting 1–2 weeks before clipping (1K1C-D; 1K-D); the other half were pair-fed (1K1C-C; 1K-C). Serum digoxin levels averaging 488 ng/ml were documented in rats receiving digoxin. After 3–5 weeks of hypertension (conscious tail blood pressures), and at a similar time period in normotensive control rats, we measured direct femoral arterial pressure and weighed standardized segments of the thoracic aorta. At sacrifice body weights of the four groups did not differ. In the one-kidney control rats, mean ± SE femoral arterial pressure (1K-D, 108 ± 3; 1K-C, 111 ± 4, mm Hg), thoracic aortic dry weight (1K-D, 36.6 ± 0.6; 1K-C, 36.2 ± 1.1. mg/kg body wt), and aortic water content (1K-D, 62.7 ± 0.4; 1K-C, 62.4 ± 0.4,% wet weight) did not differ between rats receiving or not receiving digoxin, respectively. As compared with pooled normotensive control rats, femoral arterial pressure (1K1C-D, 165 ± 8; 1K1C-C, 153 ± 5), aortic water content (1K1C-D, 64.8 ± 0.4; 1K1C-C, 64.9 ± 0.5), and aortic weight (1K1C-D, 44.8 ± 2.1; 1K1C-C, 50.1 ± 1.6) were increased (P < 0.001) in the one-kidney, one-clip rats, on or off digoxin. Comparison of hypertensive rats receiving to those not receiving digoxin revealed no differences in arterial pressure or aortic water content, but aortic growth was significantly attenuated (-41%, P = 0.02) in the hypertensive rats receiving digoxin. These results provide evidence that digoxin reduces hypertensive arterial growth by a mechanism that does not affect normal growth.