Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers

The maternal circulation vasodilates during pregnancy. We investigated the contribution of nitric oxide to this vasodilatation. Using venous occlusion plethysmography, we measured the effect of nitric oxide synthase inhibition on hand blood flow during human pregnancy. We compared the response to a brachial artery infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) with the response to norepinephrine in three groups of women: nonpregnant, early pregnant (9-15 wk), and late pregnant (36-41 wk). Basal hand blood flow increased significantly during late pregnancy compared with nonpregnant and early pregnant subjects (P = 0.007). L-NMMA produced a greater reduction in hand blood flow in both pregnant groups compared with nonpregnant controls (P = 0.0003). Norepinephrine produced an attenuated response in late pregnancy compared with nonpregnant and early pregnant women (P = 0.0029). If other vascular beds respond in the same way as the hand, the gestational increase in vasoconstrictor response to L-NMMA that we observed implicates increased generation of nitric oxide in the fall of peripheral vascular resistance during healthy human pregnancy.

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Functional Effects of Endothelial Nitric Oxide Synthase Genetic Polymorphisms on Haemorheological Parameters in Healthy Human Individuals

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/j.1742-7843.2010.00637.x ◽

2010 ◽

Vol 108 (3) ◽

pp. 171-176 ◽

Cited By ~ 2

Author(s):

Melih O. Babaoglu ◽

Neslihan Dikmenoglu ◽

Esin Ileri-Gurel ◽

Nurten Seringec ◽

Teuta Zoto ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Genetic Polymorphisms ◽

Endothelial Nitric Oxide Synthase ◽

Healthy Human ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans

Cardiovascular Research ◽

10.1093/cvr/cvab155 ◽

2021 ◽

Author(s):

Kevin O’Gallagher ◽

Francesca Puledda ◽

Owen O’Daly ◽

Matthew Ryan ◽

Luke Dancy ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Functional Connectivity ◽

Nitric Oxide Synthase ◽

Neuronal Nitric Oxide Synthase ◽

Healthy Human ◽

Brain Functional Connectivity ◽

Oxide Synthase

Abstract Aims Neuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signaling is implicated in cerebrovascular ischemia and migraine. Previous human studies have investigated the effects of non-selective NOS inhibition but there has been no direct investigation of the role of nNOS in human cerebrovascular regulation. We hypothesised that inhibition of the tonic effects of nNOS would result in global or localized changes in cerebral blood flow, as well as changes in functional brain connectivity. Methods and Results We investigated the acute effects of a selective nNOS inhibitor, S-methyl-L-thiocitrulline (SMTC), on cerebral blood flow and brain functional connectivity in healthy human volunteers (n=19). We performed a randomised, placebo-controlled, crossover study with either intravenous SMTC or placebo, using magnetic resonance imaging protocols with arterial spin labelling and functional resting state neuroimaging. Conclusions These data suggest a fundamental physiological role of nNOS in regulating regional cerebral blood flow and functional connectivity in the human hippocampus. Our findings have relevance to the role of nNOS in the regulation of cerebral perfusion in health and disease. Translational Perspective Animal models have implicated dysfunctional nNOS-mediated signaling in neurovascular and neurodegenerative conditions. This first study of the effects of a selective nNOS inhibitor, S-methyl-thiocitrulliune (SMTC), on the physiological regulation of human cerebral blood flow and brain functional connectivity opens the way to investigation of the effects of nNOS in cerebrovascular disease states. We also demonstrate that an acute infusion of SMTC is safe yet biologically active within the healthy human brain. The therapeutic potential of modulating the nNOS pathway in the brain could now be investigated; e.g. whether inhibition of nNOS activity is valuable in settings of post-ischemia excitotoxicity.

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Localization of endothelial nitric oxide synthase in the normal and failing human atrial myocardium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166397 ◽

1996 ◽

Vol 54 ◽

pp. 786-787

Author(s):

Chi-Ming Wei ◽

Margarita Bracamonte ◽

Shi-Wen Jiang ◽

Richard C. Daly ◽

Christopher G.A. McGregor ◽

...

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Cardiac Tissues ◽

Mammalian Tissues ◽

End Stage Heart Failure ◽

End Stage ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Nitric oxide (NO) is a potent endothelium-derived relaxing factor which also may modulate cardiomyocyte inotropism and growth via increasing cGMP. While endothelial nitric oxide synthase (eNOS) isoforms have been detected in non-human mammalian tissues, expression and localization of eNOS in the normal and failing human myocardium are poorly defined. Therefore, the present study was designed to investigate eNOS in human cardiac tissues in the presence and absence of congestive heart failure (CHF).Normal and failing atrial tissue were obtained from six cardiac donors and six end-stage heart failure patients undergoing primary cardiac transplantation. ENOS protein expression and localization was investigated utilizing Western blot analysis and immunohistochemical staining with the polyclonal rabbit antibody to eNOS (Transduction Laboratories, Lexington, Kentucky).

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