Differential effects of oral losartan and enalapril on local venous and systemic pressor responses to angiotensin I and II in healthy men.
This double-blind, placebo-controlled crossover study was designed to differentiate the pharmacodynamic effects of the angiotensin II receptor antagonist losartan from the angiotensin converting enzyme inhibitor enalapril. Effects of placebo, enalapril (10 mg), and losartan (20 and 100 mg) on local venous and systemic pressor responses to angiotensin I and II were compared in eight healthy male subjects. Treatments were administered orally approximately 4 hours before agonist infusions into a dorsal hand vein. Local changes in hand vein diameter and systemic blood pressure were monitored during the infusions. The 100 mg dose of losartan attenuated local venoconstrictor and systemic pressor responses to angiotensin I and II. In contrast, enalapril blocked only responses to angiotensin I. Both losartan and enalapril increased plasma renin concentration compared with placebo. These results are consistent with direct antagonism of angiotensin II receptors by losartan and with indirect effects of enalapril through inhibition of angiotensin converting enzyme.
Merck Research Laboratories, West Point, PA 19486, USA.
M R
MR
Goldberg
C
C
de Mey
J M
JM
Wroblewski
Q
Q
Li
V
V
Schroeter
G G
GG
Belz
D000284:Administration, Oral; D000328:Adult; D000803:Angiotensin I / Q000037:antagonists & inhibitors*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology*; D006225:Hand / Q000098:blood supply; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D012016:Reference Values; D012083:Renin / Q000097:blood / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D012083:Renin; D019808:Losartan