Acute hypertensive pulmonary edema: a new paradigm

2010 ◽  
Vol 88 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Lincoln E. Ford

Although acute hypertensive pulmonary edema is sometimes regarded as the most severe form of heart failure, at the peak of symptoms, hearts perform well above resting levels and cannot be said to be failing. Another characteristic of the condition, the rapidity of its onset and reversal when properly treated, suggests positive feedback as a causal mechanism. It is proposed that the syndrome results from a feedback loop with increased sympathetic tone as the efferent output, increased pulmonary vascular pressure as the stimulus to increased sympathetic tone, and positive feedback occurring because elevated sympathetic tone constricts systemic veins, thereby transferring blood from peripheral veins to the pulmonary vasculature. Evidence for the proposed mechanism derives from all the empirical treatments that have evolved. All remove blood from the pulmonary circuit, and all but the oldest, bloodletting, do so by transferring blood from the pulmonary circuit to the peripheral veins.

2016 ◽  
Vol 30 (3) ◽  
pp. 372-381 ◽  
Author(s):  
Malika Jafferjee ◽  
Thairy Reyes Valero ◽  
Christine Marrero ◽  
Katie A. McCrink ◽  
Ava Brill ◽  
...  

Abstract Elevated sympathetic nervous system (SNS) activity aggravates several diseases, including heart failure. The molecular cause(s) underlying this SNS hyperactivity are not known. We have previously uncovered a neurohormonal mechanism, operating in adrenomedullary chromaffin cells, by which circulating catecholamine (CA) levels increase in heart failure: severe dysfunction of the adrenal α2-adrenergic receptors (ARs) due to the up-regulation of G protein-coupled receptor-kinase (GRK)-2, the kinase that desensitizes them. Herein we looked at the potential signaling mechanisms that bring about this GRK2 elevation in chromaffin cells. We found that chronic CA treatment of either PC12 or rat primary chromaffin cells can in itself result in GRK2 transcriptional up-regulation through α2ARs-Gi/o proteins-Src-ERK1/2. The resultant GRK2 increase severely enhances the α2AR desensitization/down-regulation elevating not only CA release but also CA biosynthesis, as evidenced by tyrosine hydroxylase up-regulation. Finally, GRK2 knockdown leads to enhanced apoptosis of PC12 cells, indicating an essential role for GRK2 in chromaffin cell homeostasis/survival. In conclusion, chromaffin cell GRK2 mediates a positive feedback loop that feeds into CA secretion, thereby enabling the adrenomedullary component of the SNS to turn itself on.


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