Sen. Mary Landrieu (D-La.) may have put herself in even tougher political straits in 2008 after casting a key vote last week that defied her most powerful and perhaps only GOP Senate ally, Minority Whip Trent Lott (Miss.).

Republican Senate sources say all bets appear to be off for playing nice with Landrieu since she bucked the GOP — and Lott in particular — in deciding to vote against allowing a confirmation vote on Leslie Southwick to the New Orleans-based 5th U.S. Circuit Court of Appeals. While Southwick ended up securing the controversial installment with bipartisan support, several GOP sources said it came without Landrieu’s previously promised support to Lott, who was whipping his colleagues for his home-state judicial pick.

“A deal like that was so personal and important to Sen. Lott — and he does have a long memory,” said one Republican Senator, speaking on the condition of anonymity because of the sensitivity of the issue. “The protocol in the Senate is at least to notify the person you promised the vote to. It’s not a very smart play.”

Lott’s office declined to comment, but several Senate sources said the Minority Whip and Landrieu shared an exchange off the floor following her vote to block the Southwick nomination from advancing. Those sources said Lott felt blindsided by her opposition and afterward indicated to his fellow Republican colleagues that he no longer would look to shield her from political attacks heading into next year’s election.

“He gave the green light,” said a senior Republican staffer.

Adam Sharp, spokesman for Landrieu, acknowledged Tuesday that “Sen. Lott was not happy with her vote,” but he dismissed as “overblown” any talk of a falling out between the pair. Sharp said Landrieu and Lott have long enjoyed a strong working relationship and one vote will not destroy that.

“There will always be disagreements in any friendship, and times when [friends] are upset with each other and move on,” Sharp said. “There’s no doubt that will happen here.”

Indeed, Lott and Landrieu long have shared a cross-party alliance, particularly on issues relating to the Gulf Coast region in the wake of Hurricane Katrina, which devastated both of their home states. Lott is known to regularly broker deals with Landrieu and, at times, looks to soften his party’s efforts to undercut her politically.

“Lott protects her sometimes,” noted a Republican leadership aide. “But she voted against Southwick after making a commitment [to vote for him]. If [Lott] isn’t standing in between her and the fire, she’s going to get the full force of it.”

It’s unclear how Lott’s ire over the Southwick vote will translate into tougher GOP campaigning against Landrieu, whom Republicans view as their best chance to unseat a sitting Senator this cycle. Perhaps not coincidentally, the National Republican Senatorial Committee attacked Landrieu on two fronts last week — both on her Southwick vote and on her position on extending the Internet tax moratorium.

At the same time, Landrieu appears to have the full weight of a powerful Democratic majority behind her — one that certainly will offer up its bank account and provide opportunities for her to take a leading role on issues such as Katrina recovery. What’s more, Landrieu has been preparing for her re-election for months, and those close to her say she’s not naive about the challenges ahead.

“She’s a real street fighter,” said Jim Manley, spokesman for Majority Leader Harry Reid (D-Nev.). “She knows full well what she’s got to do to get re-elected next year. Obviously, like any of our incumbents, we’ll do whatever we can” to help her.

Asked whether Landrieu expects an even tougher beating from the GOP following the Southwick vote, Sharp asked: “Were the gloves ever on?

“This is going back many months so, you know, I don’t think the Republican Party organization was waiting for a permission slip from Sen. Lott to go after their avowed No. 1 target.”

It’s no secret the Southwick confirmation was a personal one for Lott, who spent weeks trying to round up votes for the Mississippi appellate court nominee. Lott teamed up with moderate Democratic Sen. Ben Nelson (Neb.) by holding a series of meetings with deal-minded Senators to ensure enough Democrats would agree to bring Southwick to the floor for an up-or-down vote, and in so doing, sidestep a Democratic filibuster.

In the end, 13 Democrats joined 49 Republicans to advance the confirmation. Of those Senators, 59 agreed to install Southwick to the lifetime federal appointment. Landrieu voted no on both ballots, saying that after much consideration she didn’t believe Southwick was the appropriate fit for the Southern-based court.

“When the citizens of my state head to the 5th Circuit with the cards already stacked against them, they need a judge who will deal a fair hand,” Landrieu said last week. “So, I view this vote about the needs and future of this court. Whatever Judge Southwick’s credentials, with hundreds of exemplary lawyers and judges to choose from, I do not think he meets the needs for this circuit.”

The GOP Senator said that given Louisiana voted last week to elect a Republican governor in Rep. Bobby Jindal, it is curious as to why Landrieu would turn a blind eye to “what [GOP] friends you do have.”

“Far be it for me to know what animates people’s actions,” said the Senator. “But it was not the smartest play.”