Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave.
BACKGROUND
Deficiency of nitric oxide (NO) production has been implicated in the pathogenesis of increased pulse wave reflection associated with systolic hypertension. We investigated the effects on systolic blood pressure (BP) and pulse wave contour of two nitrate donors, isosorbide mononitrate (ISMN) and L-arginine.


METHODS
The subjects were 14 elderly patients chronically treated with antihypertensive agents. In seven of the subjects, agents causing angiotensin II (AII) inhibition (angiotensin-converting enzyme [ACE] inhibitor or AT(1) receptor antagonist, or both) were used. Study entry required systolic BP of 150 to 200 mm Hg, and aortic pulse wave augmentation more than 15 mm Hg. Pharmacodynamic responses to ISMN, L-arginine, and ISMN plus L-arginine, were assessed in double-blind crossover studies by standard sphygmomanometry and applanation tonometry.


RESULTS
Peripheral systolic BP, aortic systolic BP, and the aortic augmentation index were decreased (P <.001) by ISMN, irrespective of AII inhibition. L-arginine enhanced these effects (P <.001) in the subjects without AII inhibition, but not in those receiving AII inhibitors. Given without ISMN or AII inhibitors, L-arginine decreased peripheral systolic BP, but to a lesser extent than ISMN.


CONCLUSIONS
L-arginine has potential value as an adjunct to ISMN in combination with antihypertensive therapy in elderly patients with systolic hypertension. However, when given with single-dose ISMN, its vasodilator activity may overlap with that of AII inhibitors. Future studies of L-arginine in conjunction with chronic continuous ISMN dosing are warranted.
Stokes
Gordon S
GS
Hypertension Unit, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. gstokes@med.usyd.edu.au
Barin
Edward S
ES
Gilfillan
Kerry L
KL
Kaesemeyer
Wayne H
WH
D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D018592:Cross-Over Studies; D003971:Diastole / Q000187:drug effects; D004311:Double-Blind Method; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D011187:Posture; D011674:Pulse; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001120:Arginine; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate