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 greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 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.
Anderson
P W
PW
Department of Internal Medicine, Los Angeles County University of Southern California Medical Center.
Do
Y S
YS
Schambelan
M
M
Horton
R
R
Boger
R S
RS
Luther
R R
RR
Hsueh
W A
WA
D000328:Adult; D000450:Aldosterone / Q000097:blood; D004151:Dipeptides / Q000627:therapeutic use* / Q000652:urine; D011464:Epoprostenol / Q000652:urine; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D000092502:Renin Inhibitors
D000450:Aldosterone; D004151:Dipeptides; D011464:Epoprostenol; D012083:Renin; D000092502:Renin Inhibitors; C056622:enalkiren