Amelioration of effects of hypertension and diabetes on myocardium by cardiac glycoside

Abstract

To determine whether digoxin protects the myocardium during the initial phases of hypertension and diabetes combined, adult male Wistar rats with two-kidney, one-clip renal hypertension and streptozotocin-induced diabetes mellitus were treated with digoxin (500 micrograms.kg-1.day-1) by gavage for 10 wk immediately after the onset of hypertension and diabetes. Systemic arterial blood pressures, ventricular pressures, the first time derivative of left ventricular pressure, diastolic wall stress, and the quantitative analysis of the number and distribution of myocardial lesions and capillary density of the myocardium were measured. In comparison to untreated hypertensive-diabetic animals, digoxin-treated rats showed a lesser elevation in left ventricular end-diastolic pressure and diastolic and systolic wall stress despite comparable degrees of hypertension and blood glucose levels. In addition, chamber diameter was smaller and the diffusion distance for oxygen was within normal values in animals treated with this glycoside. However, the numerical density of the foci of replacement fibrosis was similar to that found in untreated hypertensive-diabetic animals. In conclusion, digoxin reduces the magnitude of ventricular remodeling and diastolic wall stress in this model of hypertension and diabetes.

Ouabain-induced hypertension enhances left ventricular contractility in rats

“…If we compared the present results with results performed using microtip pressure transducers we observed that the present values obtained with polyethylene catheter are lower when compared to those obtained with the microtip catheter (Capasso et al, 1992;Pacher et al, 2004;Samsamshariat et al, 2005). However, the results using the microtip catheter are commonly performed in anesthetized rats.…”

Long-term ouabain administration produces hypertension in rats.

“…Longterm digoxin administration has been shown to reduce ventricular remodeling and diastolic wall stress in hypertensive two-kidney, one clip diabetic rats. 47 Relative adrenal mass was significantly less in 60% RRM rats treated with ouabain, whereas that of 2-K, 25% RRM, and 70% RRM animals was unchanged compared with controls. The significance of this is unclear, although it is tempting to speculate that the situation seen here may be analogous to that seen during administration of exogenous corticosteroids.…”

A Novel Inexpensive Murine Model of Oral Chronic Digitalization

“…In addition, to the best of our knowledge the effect of chronic cardiac glycosides on dP/dt, an index of contractility, seems to be the first in vivo rat data published. It is of note that, in a similar assay in rats treated by gavage with digoxin (500 µg/kg per day), no increase in dP/dt was described 12 . Furthermore, we want to emphasize the absence of detectable side‐effects in treated animals in the present study, including on electrocardiographic evaluation.…”

“…It is of note that, in a similar assay in rats treated by gavage with digoxin (500 g/kg per day), no increase in dP/dt was described. 12 Furthermore, we want to emphasize the absence of detectable side-effects in treated animals in the present study, including on electrocardiographic evaluation. Another and no less important aspect of the present study is the ease of administration of the drug and the low cost of the method, which allows an investigator to dispense with more sophisticated and expensive systems, such as mini-pumps.…”