(CNN) -- Voters sent mixed signals in Tuesday's primary elections in Pennsylvania, Kentucky and Arkansas. They tossed out a veteran senator, nominated a Tea Party-backed candidate and also chose a longtime aide to fill the U.S. House seat vacated by the death of Democratic Rep. John Murtha.
In another closely watched race, Democratic Sen. Blanche Lincoln failed to win more than 50 percent of the vote and faces a June 8 runoff in the Arkansas Senate primary to decide the party's candidate in November.
The results reinforced the perception of anger across the country against Washington politics-as-usual, but also showed the public discontent may be aimed at both Democrats and Republicans.
In Pennsylvania, voters rejected longtime incumbent Sen. Arlen Specter's bid to run for a sixth Senate term, choosing Rep. Joe Sestak as the Democratic nominee for Senate in November.
Specter, 80, was a Republican until he crossed party lines last year to cast a deciding vote on President Obama's stimulus plan. Soon after, he changed parties in the face of plummeting GOP support in his primary battle against Pat Toomey, a former member of Congress and head of the conservative group Club for Growth.
Sestak called his victory "a win for the people, over the establishment, over the status quo, even over Washington, D.C."
Despite support from Obama and other top Democrats, Specter lost to Rep. Joe Sestak, a retired Navy admiral who made up a big deficit in the polls. Sestak focused his campaign on Specter's party switch after almost 30 years in the Senate as a Republican.
In conceding defeat, Specter pledged his support to help Sestak defeat Toomey.
"Some want to go back to the failed policies of George Bush," Sestak said in apparent reference to his GOP foe in November. "Letting Wall Street do whatever it wants or just say no to progress. On the other hand, I think we know we're in pretty tough times, but we know that we can go forward, we know that we must go forward. But to do so we need a public servant, not a politician."
Also in Pennsylvania, Democrat Mark Critz defeated GOP businessman Tim Burns in a special election to fill the House seat held for more than three decades by Murtha, who died in February. Critz worked for Murtha and has vowed to continue his legacy if elected to complete Murtha's term. He will have to defend the seat in November.
While Murtha rarely had any serious challenges in his 18 re-election contests, his party doesn't dominate what's considered a socially conservative district that stretches from Cambria County in west-central Pennsylvania to the southwestern corner of the state.
The high-profile race brought big names to the district, with former President Bill Clinton campaigning for Critz and Sen. Scott Brown, R-Massachusetts, appearing on the campaign trail for Burns.
The primary races came in the wake of some recent tough blows to sitting lawmakers: Sen. Bob Bennett, a three-term senator, failed to advance at the Utah GOP convention, and Rep. Alan Mollohan didn't win over fellow Democrats in last week's West Virginia primary.
In the first race called Tuesday night, conservative insurgent Rand Paul -- son of former GOP presidential candidate and Texas Rep. Ron Paul -- defeated Secretary of State Trey Grayson in Kentucky's Republican primary fight for the seat held by retiring GOP Sen. Jim Bunning. With more than half the votes counted, Paul had about 60 percent of the total.
Paul, a physician, had the backing of some Tea Party groups and was endorsed by former Alaska Gov. Sarah Palin. He will face Kentucky Attorney General Jack Conway, the winner of the Democratic primary, in the November election.
"We've come to take our government back," Paul said in his victory speech. "This Tea Party movement is a message to Washington that we're unhappy and that we want things done differently."
Grayson was the establishment candidate in the race, using the backing of Kentucky's senior senator, Minority Leader Mitch McConnell, to be the early favorite.
McConnell quickly congratulated Paul on his victory and signaled full party support for him in the November Senate race.
"Now Kentucky Republicans will unite in standing against the overreaching policies of the Obama administration," McConnell said in a statement. "We are spiraling further into unsustainable debt, and Kentucky needs Rand Paul in the U.S. Senate because he will work every day to stop this crippling agenda."
Analysts said Tuesday's results could foreshadow the mood of voters in the November midterm election.
"Is this a referendum on national politics? I think so," said Joe DiSarro, chairman of the political science department at Washington & Jefferson College in Washington, Pennsylvania.
"Is it something that we can say is a prelude to the fall? Oh, yes," he added.
In Arkansas, Lincoln held a steady lead in the Senate Democratic primary over Lt. Gov. Bill Halter, but neither was able to secure enough support to avoid a runoff. Halter, who has the backing of unions and several key progressive groups, has repeatedly blasted Lincoln for not supporting a government-run public option during the congressional health care debate.
Stu Rothenberg, publisher of the nonpartisan Rothenberg Political Report, says many liberals don't believe Lincoln, a political moderate, has been a strong enough ally for their party. Many political observers, however, question the ability of a more progressive Democrat to win statewide.
Whoever wins the Democratic primary will face a strong threat for a GOP takeover of the seat in a state that most experts believe will lean toward Republicans in November.
In the crowded GOP primary field, Rep. John Boozman held a big lead, but it was unclear if he would exceed the 50 percent threshold to avoid a runoff.
Arkansas Secretary of State Charlie Daniels said Tuesday that a record 125,000 residents had voted early or absentee in his state's primaries -- an indication of the strong general interest in what is usually a low-turnout affair.
Leaders of both parties now agree that 2010 is a tough year for experienced politicians.
"There is no question. There is, at this moment, an anti-incumbent mood," House Speaker Nancy Pelosi, D-California, recently said.
House Minority Leader John Boehner, R-Ohio, concurred. This year, "It's politicians beware," he warned.
CNN's Kevin Bohn, Alan Silverleib, John Helton, Ed Hornick, Kristi Keck, Charles Riley and Paul Steinhauser contributed to this report.