RENAL VASCULAR-RESPONSES TO RENIN INHIBITION WITH ZANKIREN IN MEN

Renin inhibition represents an alternative to angiotensin-converting e nzyme (ACE) inhibition for pharmacologic interruption of the renin-ang iotensin system. In addition to inhibiting the formation of angiotensi n II, ACE inhibitors also inhibit the degradation of kinin and result in accumulation of powerful renal vasodilator prostaglandins and brady kinin. We were therefore surprised by the large renal vasodilator resp onse achieved with the renin inhibitor enalkiren, because substrate-sp ecific renin inhibitors reduce the formation of angiotensin II without affecting other vasodilator mechanisms. To determine whether previous findings were reflective of the renin inhibitor class, we studied 12 healthy men on a 'sodium-restricted diet, each of whom received two or three escalating oral doses of zankiren, a new agent. Plasma renin ac tivity decreased with the smallest dose (5 mg), and this effect was su stained. The increase in renal plasma how was clearly related to dose (r = 0.86, F = 9.67), reaching a maximum of 134 +/- 26 ml/min/1.73 m(2 ) at 250 mg, the highest dose. Renin inhibition exerts a remarkable re nal vasodilator action, perhaps reflecting the lipophilicity of the ag ents developed to date, an action that may have clinical implications for the prevention of renal injury in patients at risk.