Release of a contractile factor and reduced nitric oxide from isolated pulmonary resistance vessels from BalB/CJ mice cause higher reactivity to angiotensin II compared to C57BL/6J mice

Abstract

Pulmonary arterial hypertension (PAH) is caused by increased pulmonary vascular resistance that can develop as part of other pathologies such as pulmonary embolism and heart failure, or because of pulmonary vascular remodeling. The role of angiotensin II in pulmonary hypertension has not been extensively studied, and some conflicting results have been presented.We have seen that Balb/CJ mice treated with angiotensin II and high salt diet (AngII+Salt) develop increased pulmonary vascular resistance and right ventricle systolic pressure already 24 hours following treatment initiation. Within the following 6 days, Balb/CJ mice develop massive edema and heart failure. C57Bl/6J mice on the other hand are resistant to this treatment. We hypothesized that pulmonary vessels in Balb/CJ mice are more reactive to angiotensin II than in C57BL/6J mice. The aim of present study was to investigate isolated pulmonary resistance vessel reactivity in Balb/CJ and C57BL/6J mice using wire myography.The results show that pulmonary resistance vessels from Balb/CJ mice have enhanced vascular reactivity to angiotensin II, which abolished in denuded vessels. Pulmonary resistance vessels from C57BL/6J mice on the other hand show little or no response to angiotensin II. However, transfer of bath solution from Balb/CJ pulmonary vessels to C57BL/6J pulmonary vessels induces as strong contraction as in Balb/CJ mice. This indicates that angiotensin II causes increased vascular contraction in Balb/CJ mice, mainly by stimulating release of a secondary substance from the endothelium which in turn causes strong contraction. Further, acetylcholine induced relaxation is weaker in pulmonary arteries from Balb/CJ mice compared to C57BL/6J mice, while sodium nitroprusside induced relaxation does not differ between the strains indicating a difference in endothelial nitric oxide production as well.In conclusion, pulmonary artery endothelial function is different between Balb/CJ and C57BL/6J mice, causing increased vascular reactivity to angiotensin II, by stimulating release of a substance that in turn causes contraction both in BalB/CJ mice and C57BL/6J mice. In addition, Balb/CJ show reduced relaxation after acetylcholine. These results may increase the understanding of the role of angiotensin II in pulmonary hypertension, as well as shed some light on increased susceptibility to pulmonary hypertension in patients with a reactive phenotype.Support or Funding InformationSwedish Society of Medical Research, and the Swedish Heart‐Lung Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.