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Influence of captopril and enalapril on rat platelet aggregation and on platelet serotonergic mechanisms
343
El
P.mo.158
ce of
captoprill
Buczko, W., Malinowska, B., Pietraszek, M.H. and Chabielska, E. Department of Pharmaco&namics, Medical Academy, Bialystok, Poland
Inhibitors of angiotensin converting enzyme (CEI) are now established as clinically useful in therapy in the management of hypertension and heart failure. However, the mechanism, by which CEI lower blood pressure still remains to be clarified in detail. We have recently demonstrated that captopril reduced the pressor effect of 5hydroxytryptamine (SHT, serotonin) in pithed rats (MalinoTwska and Buczko, 1989). On the other hand it has been reported the suppressive effect of captopril on platelet aggregation in essential hypertension (Someya et al., 1984). However, these results were not confirmed (Schulz et al., 1986). One of the many factors which stimulate platelet aggregation is serotonin. It amplifies platelet aggregation of rats and humans via 5HT2 receptors. ‘Re serotonergic system in rat blood plat.elets also consists of a relatively specific uptake mechanism for 5HT and intracellural storage organelles. The present study was therefore designed to: 1. The study the influence of acute and chronic administration of captopril and enalapril on rat platelet aggregation. 2. examine if the effect of captopril and enalapril is dependent on serotonergic mechanisms in blood platelets. The experiments were performed on male normotensive Wistar rats. We demonstrated that both acute (10 mg/kg, days, p.o.) captopril adminic.~ation significantly reduced ADP (4 ahI) P.O., -30 m.i$ and chronic (10 mg/kg/7 induced rat platelet aggregation from lOt!.!% to 7.6.0 f 8.5 and 79.5 f 6.38, respectively. In contrast, the reduction of platelet aggregation was not observed when rats were pretreated with a single dose OCenalapril(l0 mg/kg, p-o., -60 mitt) or chronically (30 mg/kg/7 days, p.0.). 5HT (lo-* M) significantly amplified ADP induced platelet aggregation by about 25%. This amplifying effect of 5HT was not changed in all studied groups of animals. The uptake of labelled serotonin in control rats was 183.3 f 15.3 pmol/min/109 platelets. Acute and chronic administration of captopril and enalapril did not affect this studied parameter. We also did not observe the changes of concentration of 5HT (0.90 f 0.20 pg/lO’ platelets in control group; 0.90 f 0.20 and 0.97 f 0.20 pg/109 platelets in rats acutely and chronically pretreated with captopril; 0.83 f 0.04 and 0.89 f 0.12 in aGnals acutely and chronically pretreated with enalapril). Conclusion: 1. Captopril causes ex vivo the suppression of rat platelet aggregation. This action is not dependent on serotonergic mechanisms in blood platelets. 2. Enalapril did not influence ex vivo rat platelet aggregation and platelet serotonergic mechanisms.
References Malinowska,B. and W. Buczko, 1989, Pharmacology 38,273. Schulz, V., W. Fischsr, V. Hausell and V. Zieisch, 1986, Eur. J. Clin. Phannacol. 31.411. Someya, N., Y. Morotomi, K. Kodama, 0. Kida. T. Higa, K. Kondo and K. Tan&a, 1984, J. Cardiovasc. Pharmacol. 6,840.
El
P.mo.158
ce of
captoprill
Buczko, W., Malinowska, B., Pietraszek, M.H. and Chabielska, E. Department of Pharmaco&namics, Medical Academy, Bialystok, Poland
Inhibitors of angiotensin converting enzyme (CEI) are now established as clinically useful in therapy in the management of hypertension and heart failure. However, the mechanism, by which CEI lower blood pressure still remains to be clarified in detail. We have recently demonstrated that captopril reduced the pressor effect of 5hydroxytryptamine (SHT, serotonin) in pithed rats (MalinoTwska and Buczko, 1989). On the other hand it has been reported the suppressive effect of captopril on platelet aggregation in essential hypertension (Someya et al., 1984). However, these results were not confirmed (Schulz et al., 1986). One of the many factors which stimulate platelet aggregation is serotonin. It amplifies platelet aggregation of rats and humans via 5HT2 receptors. ‘Re serotonergic system in rat blood plat.elets also consists of a relatively specific uptake mechanism for 5HT and intracellural storage organelles. The present study was therefore designed to: 1. The study the influence of acute and chronic administration of captopril and enalapril on rat platelet aggregation. 2. examine if the effect of captopril and enalapril is dependent on serotonergic mechanisms in blood platelets. The experiments were performed on male normotensive Wistar rats. We demonstrated that both acute (10 mg/kg, days, p.o.) captopril adminic.~ation significantly reduced ADP (4 ahI) P.O., -30 m.i$ and chronic (10 mg/kg/7 induced rat platelet aggregation from lOt!.!% to 7.6.0 f 8.5 and 79.5 f 6.38, respectively. In contrast, the reduction of platelet aggregation was not observed when rats were pretreated with a single dose OCenalapril(l0 mg/kg, p-o., -60 mitt) or chronically (30 mg/kg/7 days, p.0.). 5HT (lo-* M) significantly amplified ADP induced platelet aggregation by about 25%. This amplifying effect of 5HT was not changed in all studied groups of animals. The uptake of labelled serotonin in control rats was 183.3 f 15.3 pmol/min/109 platelets. Acute and chronic administration of captopril and enalapril did not affect this studied parameter. We also did not observe the changes of concentration of 5HT (0.90 f 0.20 pg/lO’ platelets in control group; 0.90 f 0.20 and 0.97 f 0.20 pg/109 platelets in rats acutely and chronically pretreated with captopril; 0.83 f 0.04 and 0.89 f 0.12 in aGnals acutely and chronically pretreated with enalapril). Conclusion: 1. Captopril causes ex vivo the suppression of rat platelet aggregation. This action is not dependent on serotonergic mechanisms in blood platelets. 2. Enalapril did not influence ex vivo rat platelet aggregation and platelet serotonergic mechanisms.
References Malinowska,B. and W. Buczko, 1989, Pharmacology 38,273. Schulz, V., W. Fischsr, V. Hausell and V. Zieisch, 1986, Eur. J. Clin. Phannacol. 31.411. Someya, N., Y. Morotomi, K. Kodama, 0. Kida. T. Higa, K. Kondo and K. Tan&a, 1984, J. Cardiovasc. Pharmacol. 6,840.