L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature

Joel Gellman, Joshua Hare, Charles J. Lowenstein, Gary Gerstenblith, Vicki Coombs, Patricia Langenberg, Jeffrey A. Brinker, Jon R. Resar

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalAngiology
Volume55
Issue number1
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Microvessels
Arginine
Vascular Resistance
omega-N-Methylarginine
Pressure
Nitric Oxide Synthase
Nitric Oxide
Coronary Artery Disease
Atherosclerosis
Ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Gellman, J., Hare, J., Lowenstein, C. J., Gerstenblith, G., Coombs, V., Langenberg, P., ... Resar, J. R. (2004). L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature. Angiology, 55(1), 1-8.

L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature. / Gellman, Joel; Hare, Joshua; Lowenstein, Charles J.; Gerstenblith, Gary; Coombs, Vicki; Langenberg, Patricia; Brinker, Jeffrey A.; Resar, Jon R.

In: Angiology, Vol. 55, No. 1, 01.01.2004, p. 1-8.

Research output: Contribution to journalArticle

Gellman, J, Hare, J, Lowenstein, CJ, Gerstenblith, G, Coombs, V, Langenberg, P, Brinker, JA & Resar, JR 2004, 'L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature', Angiology, vol. 55, no. 1, pp. 1-8.
Gellman J, Hare J, Lowenstein CJ, Gerstenblith G, Coombs V, Langenberg P et al. L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature. Angiology. 2004 Jan 1;55(1):1-8.
Gellman, Joel ; Hare, Joshua ; Lowenstein, Charles J. ; Gerstenblith, Gary ; Coombs, Vicki ; Langenberg, Patricia ; Brinker, Jeffrey A. ; Resar, Jon R. / L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature. In: Angiology. 2004 ; Vol. 55, No. 1. pp. 1-8.
@article{9b4c8fb06be848a0b56514d3a956cb07,
title = "L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature",
abstract = "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.",
author = "Joel Gellman and Joshua Hare and Lowenstein, {Charles J.} and Gary Gerstenblith and Vicki Coombs and Patricia Langenberg and Brinker, {Jeffrey A.} and Resar, {Jon R.}",
year = "2004",
month = "1",
day = "1",
language = "English",
volume = "55",
pages = "1--8",
journal = "Angiology",
issn = "0003-3197",
publisher = "SAGE Publications Inc.",
number = "1",

}

TY - JOUR

T1 - L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature

AU - Gellman, Joel

AU - Hare, Joshua

AU - Lowenstein, Charles J.

AU - Gerstenblith, Gary

AU - Coombs, Vicki

AU - Langenberg, Patricia

AU - Brinker, Jeffrey A.

AU - Resar, Jon R.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0347093531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347093531&partnerID=8YFLogxK

M3 - Article

C2 - 14759083

AN - SCOPUS:0347093531

VL - 55

SP - 1

EP - 8

JO - Angiology

JF - Angiology

SN - 0003-3197

IS - 1

ER -