Non-specific inhibition of pressor agents in vivo by the renin inhibitor pepstatin A.

The specificity of pepstatin A as an inhibitor of the cardiovascular actions of renin injected into anaesthetized rats has been investigated. Pepstatin A 70 micrograms/kg/min partially inhibited the pressor response to injected renin without affecting the pressor responses to injected angiotensin II, phenylephrine or vasopressin. Pepstatin A 150 micrograms/kg/min also produced partial inhibition of injected renin, but in addition caused significant inhibition of the other pressor agents. This was in contrast to the effects of the angiotensin converting enzyme inhibitor captopril, 100 micrograms/kg i.v., which caused greater inhibition of the renin pressor response than pepstatin A without affecting the pressor response to injected angiotensin II, phenylephrine or vasopressin. Finally the direct acting vasodilator hydralazine was found to have a similar non-specific inhibitory effect to pepstatin A on the pressor responses to injected pressor agents. It is concluded that pepstatin A reduces the pressor responsiveness to injected pressor agents and that this non-specific cardiovascular activity limits the usefulness of pepstatin A as a pharmacological tool to inhibit renal renin in vivo.