Perturbations in paracrine control of the circulation: Role of the endothelial-derived vasomediators, endothelin-1 and nitric oxide

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Abstract
Central to the control of vascular resistance in the systemic and pulmonary circulation and at the solid organ level is the function of the endothelial‐derived vasomediators, endothelin‐1 (ET‐1) and nitric oxide. Regulation of steady‐state levels of ET‐1 and endothelial nitric oxide synthase (eNOS) mRNAs represents an early and influential step in their biosynthesis and is highly responsive to exogenous stimuli. ET‐1 is expressed from a rapidly inducible promoter to generate a highly labile mRNA. Conversely, the eNOS promoter generates a constitutive level of a very stable mRNA and utilizes posttranscriptional mechanisms to modulate mRNA expression. The response of these genes in models of cellular activation commonly reflects a reciprocal pattern of regulation, namely, transcriptional induction of ET‐1 and destabilization of the eNOS mRNA. Elucidating the mechanisms influencing ET‐1 and eNOS mRNA is providing novel insight into endothelial gene regulation and providing opportunities for future therapeutic strategies. Microsc. Res. Tech. 60:46–58, 2003.