Effects of renin inhibition in systemic hypertension

The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for [is greater than or equal to]6 hours (11.9 [+ or -] 4 to 1.0 [+ or -] 0.6 ng angiotensin l/ml/hour, p [is less than]0.05). Mean arterial blood pressure declined gradually (108 [+ or -] 5 to 84 [+ or -] 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 [+ or -] 3.8 to 4.4 [+ or -] 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 [+ or -] 14 to 160 [+ or -] 60 pg/ml, p [is greater than]0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin [F.sub.1[alpha]]) decreased slightly, but not significantly (42 [+ or -] 10 to 33 [+ or -] 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension. (Am J Cardiol 1990;66:1342-1347)
The renin-angiotensin-aldosterone system is part of a biochemical pathway that is tightly coupled to the regulation of blood pressure. One approach to controlling hypertension (high blood pressure) is through the administration of a class of drugs called angiotensin converting enzyme (ACE) inhibitors, which block the formation of endogenous hypertensive agents. Converting-enzyme inhibition may have numerous effects, other than just blocking the conversion of angiotensin to its biologically active form. Hence, the exact mechanism by which ACE inhibitors affect their antihypertensive actions is not known. The drug enalkiren acts at an earlier point in the biochemical pathway, and it is thought that its only biologically significant action is to interfere with the enzymatic activity of renin, thus blocking the production of hypertensive byproducts. A study was carried out in eight healthy patients with essential hypertension (high blood pressure not secondary to some other identifiable factor) who were maintained on an unrestricted sodium diet. Enalkiren was administered intravenously, and blood pressure was monitored for six hours, as were blood levels of renin, angiotensin, aldosterone, and urinary levels of prostacyclin. Within 10 minutes of drug administration, blood levels of enzymatically active renin were decreased, and remained low for six hours. Blood pressure decreased, as did blood levels of aldosterone; there was a concomitant increase in the levels of biologically inactive renin. Levels of prostacyclin (one of the possible mediators of ACE inhibitor effects) were essentially unchanged. The administration of diuretics (which cause the removal of fluids from the body) increased the magnitude of the blood pressure effects. Enalkiren caused a decrease in blood pressure in the hypertensive patients solely by renin inhibition, but had no effect on prostacyclin levels. (Consumer Summary produced by Reliance Medical Information, Inc.)