Possible impact of nitric oxide on the antihypertensive effect of captopril and zaprinast

Abstract

The interaction between the renin-angiotensin system and nitric oxide (NO) is undeniable, but its nature is not fully known. This study investigated the contribution of NO to the acute hypotensive effect of captopril in conscious normotensive rats and the effect on blood pressure of dual administration of captopril and the phosphodiesterase-5 inhibitor zaprinast. In two separate experiments, rats were pretreated with the NO inhibitor L-arginine methyl ester (L-NAME) and with the NO enhancer zaprinast. Pretreatment with L-NAME attenuated and pretreatment with zaprinast potentiated the hypotensive effect of captopril. The hypotensive effect of captoril was not associated with a significant change in the plasma level of cyclic guanosine monophosphate (cGMP). These findings suggest that NO contributes to the blood pressure-lowering effect of captopril. The inability of captopril to alter plasma cGMP levels is not consistent with this view, however, and leads to the conclusion that NO contributes to the acute hypotensive effect of captopril, although the mechanism is not fully understood. Zaprinast potentiates the hypotensive effect of captopril, and an adjustment in dose should be considered when this combination is administered.

Effect of the Phosphodiesterase-5 Inhibitor Zaprinast on Ischemia-Reperfusion Injury in Rats

“…The medication was dosed based on previous work that suggested that beneficial effects on regional blood flow and cyclic mononucleotide levels without a significant reduction in mean arterial pressure could be achieved at 10 to 20 mg/kg doses. [17][18][19] It is possible that the concentration of zaprinast used in this study was too low to achieve a meaningful effect.…”