Effects of subchronic treatment with trandolapril and enalapril on cardiovascular morphologic alterations in the aged spontaneously hypertensive rat with heart failure.

The effects of a 3-month treatment period with the angiotensin-converting enzyme (ACE) inhibitors trandolapril (0.3 mg/kg/day, p.o.) and enalapril (10 mg/kg/day, p.o.) on hemodynamics, cardiac hypertrophy, and vascular structures were examined in old spontaneously hypertensive rats (SHRs) (24 months at the end of treatment) presenting with congestive heart failure. During the course of treatment, the mortality rate was lower in the two treated groups than in the control group. At the end of treatment, serum ACE activity was inhibited by 63 and 33% by trandolapril and enalapril, respectively, but the decrease in blood pressure they induced was not significant. The atrial natriuretic factor(ANF) plasma levels and cyclic GMP urine excretion were about 10-fold and 3-fold higher, respectively, in old SHRs than in old Wistar rats. These values were markedly decreased by both ACE inhibitors. The ventricular hypertrophy was greatly decreased by both compounds (-24% by trandolapril and -26% by enalapril). In the aorta, the media hypertrophy was significantly decreased and nuclear density increased to a similar extent by both ACE inhibitors. In the mesenteric artery, trandolapril treatment induced a complete regression of the media hypertrophy and a marked decrease in extracellular matrix surface. In addition, the collagen network appeared less dissociated in the treated animals. Similarly the nuclear density was increased and the surface of cell nuclei was decreased by trandolapril. Enalapril appeared much less potent on these parameters. These data demonstrate that treatment with trandolapril of aged SHRs presenting with heart failure results in an increase in survival of the animals and a marked regression of cardiac and vascular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of some slow channel blocking drugs on high affinity serotonin uptake by rat brain synaptosomes.

The effects of some slow channel blocking drugs were investigated on high affinity serotonin uptake into crude rat brain synaptosomes. Serotonin uptake was sodium-dependent and competitively inhibited by imipramine (IC50 0.6 microM, Ki 0.26 microM). Bepridil, verapamil and diltiazem produced an apparent competitive inhibition of serotonin uptake with respective IC50 of 4.8, 5.2 and 308 microM. Nitrendipine and the sodium channel blocker, lidocaine, were without effect, even at 100 microM. The mechanism of the inhibitory effect is unknown but may involve an allosteric interaction with the sodium-dependent transporter.