Endothelial Nitric Oxide Synthase-Induced Hypertrophy and Vascular Dysfunction Contribute to the Left Ventricular Dysfunction in Caveolin-1−/− Mice

2017 ◽  
Vol 33 (12) ◽  
pp. 1716-1724 ◽  
Author(s):  
Annette Ebner ◽  
Nadine Kuerbis ◽  
Aljoscha Brandt ◽  
Birgit Zatschler ◽  
Sönke Weinert ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Left Ventricular Dysfunction ◽  
Endothelial Nitric Oxide Synthase ◽  
Ventricular Dysfunction ◽  
Vascular Dysfunction ◽  
Left Ventricular ◽  
Caveolin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Chronic hypoxia induces right heart failure in caveolin-1−/− mice

2012 ◽  
Vol 302 (12) ◽  
pp. H2518-H2527 ◽  
Author(s):  
J. Agustin Cruz ◽  
Eileen M. Bauer ◽  
Andres I. Rodriguez ◽  
Archana Gangopadhyay ◽  
Nabil S. Zeineh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Chronic Hypoxia ◽  
Left Ventricular ◽  
Caveolin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Rv Function

Caveolin-1 (Cav-1)−/− mice develop mild pulmonary hypertension as they age. In this study, we sought to determine the effect of chronic hypoxia, an established model of pulmonary hypertension, on young Cav-1−/− mice with no measurable signs of pulmonary hypertension. Exposure of Cav-1−/− mice to chronic hypoxia resulted in an initial rise in right ventricular (RV) systolic pressure (RVSP) similar to wild-type (WT) mice. By three weeks RVSP decreased in the Cav-1−/− mice, whereas it was maintained in WT mice. The drop in RVSP in Cav-1−/− mice was accompanied by decreased cardiac output, increased RV hypertrophy, RV interstitial fibrosis, decreased RV sarco(endo)plasmic reticulum Ca2+-ATPase 2a mRNA and decreased RV function compared with WT mice. Importantly, minimal differences were noted in pulmonary vascular remodeling between WT and Cav-1−/− mice, and left ventricular function was normal in hypoxic Cav-1−/− mice. Mechanistically, increased endothelial nitric oxide synthase uncoupling and increased tyrosine nitration of protein kinase G were detected in the RV of Cav-1−/− mice. These hemodynamic, histological, and molecular changes were prevented in Cav-1−/− mice expressing an endothelial-specific Cav-1 transgene or by nitric oxide synthase inhibition. These data suggest that, in Cav-1−/− mice, increased oxidative/nitrosative stress due to endothelial nitric oxide synthase uncoupling modifies the response of the RV to pressure overload, accelerating the deterioration of RV function.

scholarly journals Hypercholesterolemia Promotes a CD36-dependent and Endothelial Nitric-oxide Synthase-mediated Vascular Dysfunction

2002 ◽  
Vol 277 (26) ◽  
pp. 23525-23533 ◽  
Author(s):  
Jeanie F. Kincer ◽  
Annette Uittenbogaard ◽  
James Dressman ◽  
Theresa M. Guerin ◽  
Maria Febbraio ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Vascular Dysfunction ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals The Key Role of Caveolin-1 in Estrogen-Mediated Regulation of Endothelial Nitric Oxide Synthase Function in Cerebral Arterioles In vivo

2001 ◽  
Vol 21 (8) ◽  
pp. 907-913 ◽  
Author(s):  
Hao-Liang Xu ◽  
Elena Galea ◽  
Roberto A. Santizo ◽  
Verna L. Baughman ◽  
Dale A. Pelligrino
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Functional Activity ◽  
Endothelial Nitric Oxide Synthase ◽  
Down Regulation ◽  
Caveolin 1 ◽  
Cerebral Arterioles ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The marked impairment in cerebrovascular endothelial nitric oxide synthase (eNOS) function that develops after ovariectomy may relate to the observation that the abundance of cerebral vascular eNOS and its endogenous inhibitor, caveolin-1, vary in opposite directions with chronic changes in estrogen status. The authors endeavored, therefore, to establish a link between these correlative findings by independently manipulating, in ovariectomized female rats, eNOS and caveolin-1 expression, while monitoring agonist (acetylcholine)-stimulated eNOS functional activity. In the current study, the authors showed that individually neither the up-regulation of eNOS (through simvastatin treatment), nor the down-regulation of caveolin-1 (through antisense oligonucleotide administration) is capable of restoring eNOS function in pial arterioles in vivo in these estrogen-depleted rats. Only when eNOS up-regulation and caveolin-1 down-regulation are combined is activity normalized. These results establish a mechanistic link between the estrogen-associated divergent changes in the abundance of caveolin-1 and eNOS protein and eNOS functional activity in cerebral arterioles.

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