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(Circulation Research. 2003;93:586.)
© 2003 American Heart Association, Inc.

Editorials

Brain in the Brawn

The Neuronal Nitric Oxide Synthase as a Regulator of Myogenic Tone

Ingrid Fleming

From the Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany.

Correspondence to Dr Ingrid Fleming, Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt/Main, Germany. E-mail fleming@em.uni-frankfurt.de

Key Words: neuronal nitric oxide synthase • 20-hydroxyeicosatetraenoic acid • plasma membrane calcium ATPase • myogenic contraction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Nitric oxide (NO) plays a central role in the regulation of cardiovascular homeostasis and is involved in the regulation of vascular tone and cardiac contractility as well as gene expression and cell proliferation. Furthermore, NO modulates renin secretion and salt and fluid reabsorption in the kidney.¹ Three isoforms of NO synthase (NOS) have been identified, the neuronal NOS (nNOS or NOS I), the inducible NOS (iNOS or NOS II), and the endothelial NOS (eNOS or NOS III). While all of these enzymes potentially affect blood pressure, only eNOS-deficient mice are hypertensive.^2,3

Although nNOS is expressed in cardiac myocytes,^4,5 as well as in vascular smooth muscle cells,^6–8 relatively little is known about the role played by nNOS-derived NO in cardiovascular homeostasis. Both pro- and antihypertensive actions have been attributed to nNOS, and selective inhibitors of this isoform have been reported to normalize blood pressure,⁹ as well as to attenuate flow-induced vasodilatation in eNOS^-/- mice.⁸

The regulation of nNOS activity, like that of eNOS, is determined by phosphorylation of the enzyme as well as by its association with a number of regulatory proteins.¹⁰ One protein that associates with nNOS in human embryonic kidney (HEK293) cells and is reported to play a major role in regulating the activity of the Ca²⁺-dependent enzyme, is the plasma membrane Ca²⁺/calmodulin-dependent Ca²⁺-ATPase (PMCA).¹¹ The ATPase binds to nNOS via an interaction between its carboxyl terminus and the PDZ domain of nNOS. Increasing expression of the PMCA4b isoform markedly attenuates NO synthesis by nNOS, an . . . [Full Text of this Article]

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