This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Didion, S. P. Articles by Faraci, F. M. Search for Related Content PubMed PubMed Citation Articles by Didion, S. P. Articles by Faraci, F. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL NITRIC OXIDE PAPAVERINE HYDROCHLORIDE PROSTAGLANDIN F2ALPHA Related Collections Animal models of human disease Pathophysiology Cell signalling/signal transduction Endothelium/vascular type/nitric oxide Other Vascular biology

(Stroke. 2001;32:761.)
© 2001 American Heart Association, Inc.

Original Contributions

Mechanisms That Produce Nitric Oxide–Mediated Relaxation of Cerebral Arteries During Atherosclerosis

Sean P. Didion, PhD; Donald D. Heistad, MD Frank M. Faraci, PhD

From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City.

Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, E315-GH, University of Iowa College of Medicine, Iowa City, IA 52242-1081. E-mail frank-faraci{at}uiowa.edu

Background and Purpose—The first goal of the present study was to examine the hypothesis that relaxation of cerebral arteries to nitric oxide in primates is dependent on activation of soluble guanylate cyclase (sGC). The second goal was to determine whether the role of sGC in mediating responses to nitric oxide is altered in atherosclerosis.

Methods—Basilar arteries from normal and atherosclerotic monkeys were studied in vitro. After precontraction with prostaglandin F₂ (0.1 to 1 µmol/L), concentration-response curves to authentic nitric oxide (1 nmol/L to 1 µmol/L), sodium nitroprusside (10 nmol/L to 10 µmol/L; a nitric oxide donor), and papaverine (10 nmol/L to 10 µmol/L; a non–nitric oxide, non–sGC-dependent stimulus) were generated in the presence and absence of 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 and 10 µmol/L; an inhibitor of sGC). The effect of ODQ on basal tone of basilar arteries from normal and atherosclerotic monkeys was also examined.

Results—Nitric oxide, sodium nitroprusside, and papaverine produced relaxation that was similar (P>0.05) in normal and atherosclerotic monkeys. ODQ produced marked inhibition (P<0.05) of vasorelaxation in response to nitric oxide and nitroprusside but not papaverine. For example, relaxation of the basilar artery in response to nitric oxide (0.1 µmol/L) was inhibited by approximately 85% and 73% by ODQ (1 µmol/L) in normal and atherosclerotic monkeys, respectively. ODQ produced contraction of the basilar arteries, and the increase in tension to ODQ was greater in normal (2.7±0.3 g; mean±SE) than in atherosclerotic monkeys (1.4±0.4 g; P<0.05). In contrast, contraction to prostaglandin F₂ was similar in the basilar artery from normal and atherosclerotic monkeys.

Conclusions—These findings suggest that (1) relaxation of cerebral arteries in primates in response to nitric oxide is normally dependent, in large part, on activation of sGC and (2) the influence of sGC (via reduced production and/or activity of basal nitric oxide) on cerebral vascular tone is reduced in atherosclerosis.

Key Words: atherosclerosis • basilar artery • guanylate cyclase • nitric oxide • vasodilation • monkeys

This article has been cited by other articles:

				J. Kitayama, F. M. Faraci, S. R. Lentz, and D. D. Heistad Cerebral Vascular Dysfunction During Hypercholesterolemia Stroke, July 1, 2007; 38(7): 2136 - 2141. [Abstract] [Full Text] [PDF]

				C. E. Teixeira, F. B.M. Priviero, J. Todd Jr, and R. C. Webb Vasorelaxing Effect of BAY 41-2272 in Rat Basilar Artery: Involvement of cGMP-Dependent and Independent Mechanisms Hypertension, March 1, 2006; 47(3): 596 - 602. [Abstract] [Full Text] [PDF]

				C. Zimmermann and R.L. Haberl L-Arginine Improves Diminished Cerebral CO2 Reactivity in Patients Stroke, March 1, 2003; 34(3): 643 - 647. [Abstract] [Full Text] [PDF]

				S. P. Didion, M. J. Ryan, L. A. Didion, P. E. Fegan, C. D. Sigmund, and F. M. Faraci Increased Superoxide and Vascular Dysfunction in CuZnSOD-Deficient Mice Circ. Res., November 15, 2002; 91(10): 938 - 944. [Abstract] [Full Text] [PDF]

				S. P. Didion, M. J. Ryan, G. L. Baumbach, C. D. Sigmund, and F. M. Faraci Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1569 - H1576. [Abstract] [Full Text] [PDF]

				S. P. Didion and F. M. Faraci Effects of NADH and NADPH on superoxide levels and cerebral vascular tone Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H688 - H695. [Abstract] [Full Text] [PDF]