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(Hypertension. 1999;33:924-926.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Nitric Oxide Synthase Genes

Candidate Genes Among Many Others

Florent Soubrier

From INSERM U525, Hôpital Saint-Louis, Paris, France.

Correspondence to Dr Florent Soubrier, INSERM U525, Hôpital Saint-Louis, 1 Av Claude Vellefaux, 75475 Paris Cedex 10, France. E-mail soubrier@inserm.chu-stlouis.fr

	Introduction

 
Because of the complex and multiorgan origin of hypertension, the genetic approach is the preferred strategy for discovering genes predisposing to the disease, a strategy that was successful mostly for monogenic forms of the disease. Both linkage studies in families with informative markers and case-control studies with biallelic markers or putative functional variants on candidate genes were widely used.

Two studies published in this issue illustrate the interest and the limits of this approach on 2 genes responsible for the enzymatic generation of nitric oxide (NO).^{1 2} Among the multiple actions of NO, those involving the cardiovascular system were extensively documented and designate the genes coding for NO-generating enzymes as candidate genes.³

Because, in the mammalian genome, 3 genes encoding 3 different nitric oxide synthases (NOS) are responsible for enzymatic generation of NO from L-arginine in various cells and under various stimuli, the role of each gene in NO generation defines its place as a candidate gene in hypertension.

Transgenic experiments supply the best arguments that the endothelial NOS (eNOS) is a strong candidate since pharmacological inhibition of this isoform is not available. Homozygous mice for the knockout of the eNOS gene have a level of blood pressure 15 mm Hg higher than control mice, a result obtained independently by 2 groups.^{4 5} More recently, the mouse eNOS cDNA was transduced in mice under the transcriptional control of a heterologous endothelial cell–targeting promoter, the preproendothelin gene promoter.⁶ Basal systolic and diastolic blood pressure were both reduced by 20 mm Hg in . . . [Full Text of this Article]