Involvement of phosphodiesterase inhibiting property in antihypertensive action of prazosin: using platelet model
Dadkar, V.N.; Raghu, C.N.; Manikeri, S.R.
Indian Journal of Experimental Biology 20(6): 484-487
1982
ISSN/ISBN: 0019-5189 PMID: 7129544 Document Number: 194809
In vivo experiments were carried out in rats to correlate the fall in blood pressure with the inhibition of enzyme phosphodiesterase (PDE) by prazosin. PDE inhibitors reduce ADP-induced platelet aggregation and potentiate prostacyclin activity. Treatment with prazosin (0.5-4 mg/kg per day, p.o. for 3 days) produced a fall of 18 mm Hg in blood pressure and 40% inhibition of ADP-induced platelet aggregation. Both these effects showed plateau phenomena. For studying prostacyclin activity of prazosin, effect of rat aortic incubate on ADP-induced platelet aggregation was evaluated. Aortic incubate obtained from low dose prazosin treated animals showed greater anti-aggregatory activity which was not so with higher doses of prazosins. Inhibition of ADP-induced platelet aggregation and promotion of prostacyclin activity with prazosin, in doses capable of reducing blood pressure were suggestive of PDE inhibition, this being one of the mechanisms of anti-hypertensive action of prazosin.