Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus

Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus Objectives . This study sought to determine whether nitric oxide-mediated vasodilation is abnormal in patients with non-insulin-dependent diabetes mellitus. Background . Multiple investigations, both in experimental models and in patients with insulin-dependent diabetes mellitus, demonstrate impaired endothelium-dependent vasodilation. Decreased availability of endothelium-derived nitric oxide may contribute to the high prevalence of vascular disease in diabetes. Methods . Vascular reactivity was measured in the forearm resistance vessels of 21 patients with non-insulin-dependent diabetes mellitus and 23 matched healthy control subjects. No patient had hypertension or hypercholesterolemia. Each subject was protreated with aspirin to inhibit endogenous production of vasoactive prostanoids. Methacholine chloride (0.3 to 10 μg/min) was administered through a brachial artery cannula to assess vasodilation to endothelium-derived nitric oxide. Sodium nitroprusside (0.3 to 10 μg/min) was infused to evaluate vasodilation to an exogenous nitric oxide donor. Verapamil (10 to 300 μg/min) was administered to distinguish impaired nitric oxide-mediated vasodilation from general dysfunction of vascular smooth muscle. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each agent. To assess the role of vasoconstrictor prostanoids, a subset of eight diabetic subjects were reexamined in the absence of aspirin treatment. Results . Basal forearm blood flow in diabetic and nondiabetic subjects was comparable. The forearm blood flow responses to both methacholine chloride and nitroprasside were significantly attenuated in diabetic compared with nondiabetic subjects (p < 0.005 by analysis of variance for both agents). In contrast, the response to verapamil was not significantly different between the groups (p > 0.50). The forearm blood flow responses to these agents were not significantly affected by cyclooxygenase inhibition. Conclusion . Nitric oxide-mediated vasodilation is impaired in non-insulin-dependent diabetes mellitus. Vasoconstrictor prostanoids do not contribute significantly to vascular dysfunction. The attenuated response to exogenous as well as endogenous nitric oxide donors suggests that the abnormality is due to increased inactivation of nitric oxide or to decreased reactivity of the vascular smooth muscle to nitric oxide. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the American College of Cardiology Elsevier

Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus

Loading next page...
 
/lp/elsevier/impaired-nitric-oxide-mediated-vasodilation-in-patients-with-non-EbCbWgepZ9
Publisher
Elsevier
Copyright
Copyright © 1996 Elsevier Ltd
ISSN
0735-1097
D.O.I.
10.1016/0735-1097(95)00522-6
Publisher site
See Article on Publisher Site

Abstract

Objectives . This study sought to determine whether nitric oxide-mediated vasodilation is abnormal in patients with non-insulin-dependent diabetes mellitus. Background . Multiple investigations, both in experimental models and in patients with insulin-dependent diabetes mellitus, demonstrate impaired endothelium-dependent vasodilation. Decreased availability of endothelium-derived nitric oxide may contribute to the high prevalence of vascular disease in diabetes. Methods . Vascular reactivity was measured in the forearm resistance vessels of 21 patients with non-insulin-dependent diabetes mellitus and 23 matched healthy control subjects. No patient had hypertension or hypercholesterolemia. Each subject was protreated with aspirin to inhibit endogenous production of vasoactive prostanoids. Methacholine chloride (0.3 to 10 μg/min) was administered through a brachial artery cannula to assess vasodilation to endothelium-derived nitric oxide. Sodium nitroprusside (0.3 to 10 μg/min) was infused to evaluate vasodilation to an exogenous nitric oxide donor. Verapamil (10 to 300 μg/min) was administered to distinguish impaired nitric oxide-mediated vasodilation from general dysfunction of vascular smooth muscle. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each agent. To assess the role of vasoconstrictor prostanoids, a subset of eight diabetic subjects were reexamined in the absence of aspirin treatment. Results . Basal forearm blood flow in diabetic and nondiabetic subjects was comparable. The forearm blood flow responses to both methacholine chloride and nitroprasside were significantly attenuated in diabetic compared with nondiabetic subjects (p < 0.005 by analysis of variance for both agents). In contrast, the response to verapamil was not significantly different between the groups (p > 0.50). The forearm blood flow responses to these agents were not significantly affected by cyclooxygenase inhibition. Conclusion . Nitric oxide-mediated vasodilation is impaired in non-insulin-dependent diabetes mellitus. Vasoconstrictor prostanoids do not contribute significantly to vascular dysfunction. The attenuated response to exogenous as well as endogenous nitric oxide donors suggests that the abnormality is due to increased inactivation of nitric oxide or to decreased reactivity of the vascular smooth muscle to nitric oxide.

Journal

Journal of the American College of CardiologyElsevier

Published: Mar 1, 1996

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off