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Cited by 428Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionEicosanoids and Hypertension Pharmacology

Impaired Endothelium-Dependent Vasodilation in Patients With Essential Hypertension: Evidence That Nitric Oxide Abnormality Is Not Localized to a Single Signal Transduction Pathway

Panza, Julio A., García, Carlos E., Kilcoyne, Crescence M., Quyyumi, Arshed A., Cannon, Richard O.·1995·Circulation
DOI 10.1161/01.cir.91.6.1732
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Abstract

Background Patients with essential hypertension have abnormal endothelium-dependent vascular relaxation, largely related to reduced bioactivity of nitric oxide (NO). The purpose of the present investigation was to determine whether this defect is due to a deficit at the specific intracellular signal-transduction pathway level or is a consequence of a more generalized endothelial abnormality. Methods and Results The responses of the forearm vasculature to acetylcholine and bradykinin (endothelium-dependent agents that act through different signal transduction pathways) and to sodium nitroprusside (a direct dilator of vascular smooth muscle) were studied in 10 hypertensive patients (5 men, 5 women; aged 48±9 years old [mean±SD]) and 12 control subjects (6 men, 6 women; aged 48±7 years old). To determine the contribution of NO to bradykinin-induced vasodilation, the vascular responses to bradykinin were also measured after administration of NG-monomethyl-l-arginine, an arginine analogue that inhibits the synthesis of NO. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. The response to acetylcholine was significantly blunted in hypertensive patients (maximal blood flow, 7.5±2 versus 16.6±8 mL · min−1· 100 mL−1 in control subjects [mean±SD];P<.005). Similarly, the vasodilator effect of bradykinin was significantly reduced in hypertensive patients compared with control subjects (maximal blood flow, 8.7±2 versus 15.8±6 mL · min−1· 100 mL−1 in control subjects;P<.005). A significant correlation was found between the maximal blood flow with acetylcholine and that with bradykinin (r=.89). No significant differences were found between the two groups for vascular response to sodium nitroprusside.NG-monomethyl-l-arginine significantly blunted the response to bradykinin in control subjects (maximal blood flow decreased from 15.8±6 to 10.1±2 mL · min−1· 100 mL−1,P<.003). In contrast, inhibition of NO synthesis did not modify the response to bradykinin in hypertensive patients (maximal blood flow, 8.7±2 and 8.5±3 before and during infusion of NG-monomethyl-l-arginine, respectively;P=NS). As a consequence, the response to bradykinin after inhibition of NO synthesis was not significantly different between the two groups. Conclusions Patients with essential hypertension have impaired endothelium-dependent vasodilator responses to both acetylcholine and bradykinin. These findings indicate that the endothelial dysfunction in this condition is not related to a specific defect of a single intracellular signal-transduction pathway and suggest a more generalized abnormality of endothelial vasodilator function.

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  • Sepiapterin supplementation improves endothelial function in several mouse models, including atherosclerosis ApoE−/− mice, diabetes models, and obesity models.

    “Sepiapterin supplementation improves endothelial function in several mouse models, including the atherosclerosis model ApoE−/− mice (560), diabetes models (721), or obesity models (527).”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [721]

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Authors
Panza, J. A., García, C. E., Kilcoyne, C. M., Quyyumi, A. A., & Cannon, R. O.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1995-03-15
Volume
91
Issue
6
Pages
1732-1738
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.91.6.1732
OpenAlex
W2035929496
Cited by
428
References
57
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 12 · 2015: 9 · 2014: 12 · 2013: 8 · 2012: 5
FWCI
22.09
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
essential hypertension, endothelium-dependent vasodilation, nitric oxide, acetylcholine, bradykinin, L-NMMA, forearm blood flow, signal transduction, endothelial dysfunction, sodium nitroprusside, vasorelaxation, brachial artery, forearm circulation, endothelium-independent relaxation, nitric oxide synthase
MeSH terms
Acetylcholine, Adult, Arginine, Arm, Bradykinin, Female, Humans, Hypertension, Male, Middle Aged, Nitric Oxide, Nitroprusside, Regional Blood Flow, Vascular Resistance, Vasodilation, Signal Transduction, omega-N-Methylarginine

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