Search

To investigate fosinopril’s effect on the transient outward potassium current (Ito) of differing degrees of hypertrophied myocytes in the spontaneously hypertensive rat (SHR). Ten- and 24-week-old SHRs were used as models for cardiac hypertrophy. Hypertrophied ventricular myocytes were exposed to 1, 10, and 100 μmol/L fosinopril; the whole-cell patch-clamp technique was used to study the effects on the transient outward potassium current. Ito current density was decreased in SHR myocytes relative to controls (14.17 ± 0.31 and 11.62 ± 0.08 pA/pF in 10- and 24-week-old SHR versus 16.73 ± 0.15 pA/pF, p < 0.01). Higher concentrations of fosinopril (10 and 100 μmol/L) increased Ito peak current density in 10-week-old SHR myocytes compared with controls (14.92 ± 0.14 and 15.27 ± 0.13 pA/pF versus 14.17 ± 0.31 pA/pF, p < 0.01). Fosinopril increased Ito peak current density in 24-week-old SHR myocytes at all doses (12.70 ± 0.07, 13.74 ± 0.10, and 14.53 ± 0.13 versus 11.62 ± 0.08 pA/pF for controls, p < 0.01). Fosinopril had a greater Ito elevation potential on hypertrophied myocytes in 24-week-old compared with 10-week-old SHR for each dose (1.08 ± 0.09 versus 0.37 ± 0.26 pA/pF, p < 0.01; 2.13 ± 0.05 versus 0.75 ± 0.35 pA/pF, p < 0.01; 2.92 ± 0.07 versus 1.10 ± 0.40 pA/pF, p < 0.01). Fosinopril increased Ito current density in hypertrophied myocytes. This effect was more pronounced in myocytes with a greater degree of hypertrophy.

The distribution and excretion of intravenous injected3H-rhomotoxin was studied in mice. The radioactivity of3H-rhomotoxin was found to be high in gall bladder, liver and kidney, lower in thyroid gland, adrenal gland, heart and lungs, and lowest in brain. 52.4% of the drug was excreted in urine and feces within 6 h. Rhomotoxin was bound to plasma protein (60 % at 30 min) and to some extent to liver and kidney tissue.

M-mode echocardiograms were studied in 40 patients with myocardial infarction. The results we obtained indicate that both EPSSa and EPSSb are very valuable indices for evaluating LV function in patients with myocardial infarction. Accuracy of EPSSb attained in this study is identical with that of EPSSa, and, in addition, the measurement of the former is simpler. Therefore, we recommend to use EPSSb instead of EPSSa in clinical practice

The LD50 of rhomotoxin in mice was 0.522 mg/kg i.p. In dogs, its effective antihypertensive dose was 3.5µg/kg i.v. By 6 times the above dose, arrhythmias and changes of T wave occurred in most dogs, however, all these changes would disappear promptly and spontaneously. By 20 times the dose, death occurred in some dogs. By 30 times the dose, ventricular fibrillation occurred which resulted in death of all the animals. Rhomotoxin in effective antihypertensive dose decreased the contractility of the heart muscle slightly and temporarily, but it had no significant effect on respiration. Large dose (35 µg/kg) of rhomotoxin seemed to have no remarkable influence upon the functions of the liver and kidney in rabbits, nor did it do any significant damage to the heart, liver and kidney in pathological studies.