The ad declaring that "Venezuela is not a threat" comes amid mounting tensions between the two countries after President Nicolas Maduro this month accused Washington of plotting to oust him and ordered the US Embassy in Caracas to slash staffing levels.
The US has denied the accusations and in turn applied sanctions on seven Venezuelan officials it for allegedly violating human rights during anti-government protests last year.
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"It is a tyrannical and imperial order and it pushes us back into the darkest days of the relationship" between the US and Latin America.
The media outreach comes as officials in both Caracas and Washington engage in another round of rhetorical posturing.
On Capitol Hill, US senators grilled senior administration officials on what more the United States can do to defuse a deepening political and economic crisis in Venezuela.
The oil-dependent economy had widespread food shortages and the world's fastest inflation even before the recent plunge in crude prices burned a hole in the government's finances.
Alex Lee, the US deputy assistant secretary of state for Latin America, said legislative elections expected to take place in the South American country later this year will present an opportunity to reduce tensions because Venezuelans' political views will be heard.
But he emphasised that it is important for regional governments, almost all of which have rejected the US sanctions as heavy handed, to mount a robust observation mission to ensure voting results are credible.
Lee said concerns about Venezuela would be one of Obama's top priorities when he travels next month to Panama to attend the Summit of Americas.
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