L-arginine ameliorates the abnormal sympathetic response of the dysfunctional human coronary microvasculature.
A nitric oxide (NO)-related defect may contribute to abnormal coronary sympathetic responses that can cause ischemia in patients with endothelial dysfunction. Because L-arginine, the NO synthase (NOS) precursor, augments NO bioactivity, we hypothesized that L-arginine would improve dysfunctional coronary sympathetic responses. Eleven patients with atherosclerosis or its risk factors were challenged with the cold pressor test, a specific provocative test of cardiac sympathetic activity, after 3 separate and sequential intracoronary infusions, as follows: 1) Normal saline; 2) L-NMMA, a competitive inhibitor of NOS; and 3) L-arginine. Study patients exhibited abnormal microvascular responses with coronary vascular resistance (CVR) increasing by 22.3 +/- 9.7% (mean +/- 1 SEM), p < 0.01. In addition, the change in coronary blood flow (CBF) did not correlate with the change in rate pressure product (RPP), r = -0.29, p = NS, suggesting an uncoupling of CBF from cardiac work. In the presence of L-NMMA, the CVR response, 10.3 +/- 9.8%, did not differ from the baseline response, and there was no relationship between the changes in CBF and RPP, r = 0.13, p = NS. In contrast, L-arginine ameliorated the CVR response, -3.2 +/- 3.1%, p < 0.05 vs baseline response, and restored the normal correlation between the changes in CBF and RPP, r = 0.74, p < 0.01. L-arginine not only improved abnormal microvascular responses to sympathetic activation, but it also restored the coupling that normally exists between coronary blood flow and cardiac work. L-arginine warrants further investigation as a therapy for coronary artery disease.
Gellman
Joel
J
Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. joel_gellman@yahoo.com
Hare
Joshua M
JM
Lowenstein
Charles J
CJ
Gerstenblith
Gary
G
Coombs
Vicki
V
Langenberg
Patricia
P
Brinker
Jeffrey A
JA
Resar
Jon R
JR
D001120:Arginine / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D001120:Arginine