Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure.
Antihypertensive drugs can have different effects on central and brachial blood pressures, which may affect outcomes. Nitric oxide donors have acute effects on central blood pressure but have not been assessed with renin-angiotensin system blockade. Thirteen patients with prehypertensive/Stage 1 hypertension were randomized to five single-dose treatments separated by ≤4 days using a double-blind, crossover study design: angiotensin receptor blocker (ARB) losartan 100 mg, isosorbide mononitrate (ISMN) 60 mg, losartan 100 mg + ISMN 15 mg, losartan 100 mg + ISMN 60 mg, and placebo. Central and brachial blood pressures were measured throughout 10 hours. Mean placebo-subtracted decrease from baseline in augmentation index (AIx) approximately 1% for losartan 100 mg, 26% for ISMN 60 mg, 19% for losartan 100 mg + ISMN 15 mg, and 24% for losartan 100 mg + ISMN 60 mg. Administered with losartan 100 mg or alone, ISMN lowered AIx, demonstrating that acute effects of a nitrate donor are much larger than those of an ARB even when administered with an ARB. Differences from placebo were statistically significant except for losartan 100 mg. AIx is a good biomarker of acute hemodynamic effects of nitric oxide in prehypertensive/Stage 1 hypertension.
Department of Experimental Medicine, Merck Research Laboratories, Merck Sharp & Dohme Corp., Rahway, New Jersey 07065-0900, USA. rhonda_kaufman@merck.com
Rhonda
R
Kaufman
Irene
I
Nunes
James A
JA
Bolognese
Deborah L
DL
Miller
Dennis
D
Salotti
Jennifer M
JM
McCarthy
William B
WB
Smith
Gary A
GA
Herman
Peter U
PU
Feig
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001794:Blood Pressure; D001916:Brachial Artery; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D058246:Prehypertension / Q000188:drug therapy*
D047228:Angiotensin II Type 1 Receptor Blockers; D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors; D007548:Isosorbide Dinitrate; D019808:Losartan; C030397:isosorbide-5-mononitrate