digoxin and Hypertrophy

Vasospasm is a significant reason for poor clinical outcome in subarachnoid haemorrhage (SAH). One of the possible causes of vasospasm is attributed to the inhibition of Na(+)/K(+)-ATPase and increased intracellular calcium. Although digoxin, a cardiac glycoside (CG), inhibits the Na(+)/K(+)-ATPase, diverse and contradictory biological actions of CGs have also been reported. This study aimed to investigate the effect of digoxin on an experimental vasospasm after subarachnoid haemorrhage (SAH) in rats.. The rats used in the study were divided into normal, saline, SAH, and drug groups. A double-haemorrhage method was applied for the SAH groups. Normal saline or blood samples were injected into the cisterna magna. No surgical procedures were performed on the normal group. For the drug groups, daily digoxin was administered intraperitoneally after saline or blood injections. On days 3 and 7 after injections, the brains and basilar artery sections of all the groups were prepared for light-microscopic examination. The wall thickness and luminal area of the basilar artery were calculated by using medical imaging software.. Increased wall thickness and reduced vessel luminal area were conspicuously significant in the SAH groups which did not receive digoxin. In SAH groups after digoxin administration, the vessel wall thickness decreased, and no significant change was found in vessel wall thickness when compared with the normal and saline groups. The vessel luminal area was not reduced in SAH after digoxin administration.. These results suggest that digoxin administration in experimental SAH may have a beneficial effect on the protection against vasospasm. If further investigations support our results, the present study may offer a new insight into the treatment of SAH.

Topics: Animals; Basilar Artery; Digoxin; Disease Models, Animal; Enzyme Inhibitors; Hypertrophy; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial

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 less than 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.

Topics: Animals; Aorta, Thoracic; Arteries; Blood Pressure; Digoxin; Hypertension; Hypertrophy; Male; Organ Size; Rats; Rats, Inbred Strains

In the renal compensatory adaptation after the definition and the description of the fundamental phenomena of the functional compensation as well as of the structural adaptation is reported on mediator concepts and on modulations of the renal adaptation processes. Issuing from the central position of the sodium balance a mediator concept on natriuretic hormones (Auriculin and Endoxin) is developed which is supplemented by the renotropin mediator concept. The authors deal with the modulation of the renal compensatory adaptation (e.g. influences of age diet and so on). The pharmacotherapeutic modulation of the renal compensatory adaptation is discussed with regard to the stimulation of the tubulosecretory transport of foreign substances with para-amino hippuric acid as principal substance (including own investigations with cyclopenthiazide [Benesal].

Topics: Adaptation, Physiological; Animals; Atrial Natriuretic Factor; Blood Proteins; Cardenolides; Digoxin; Feeding Behavior; Glomerular Filtration Rate; Growth Substances; Humans; Hypertrophy; Intercellular Signaling Peptides and Proteins; Kidney; Kidney Function Tests; Kidney Transplantation; Nephrectomy; Saponins; Sodium-Potassium-Exchanging ATPase; Water-Electrolyte Balance

Topics: Animals; Aorta; Cardiomyopathies; Constriction; Digoxin; Heart; Hypertrophy; Myocardium; Organ Size; Rabbits; Time Factors; Tritium

Topics: Adult; Aged; Cardiomegaly; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Hypertrophy; Male; Middle Aged; Mitral Valve Stenosis; Rheumatic Heart Disease; Vectorcardiography