Bryce Harper (2 for 3) takes third base on a fly ball in the second inning as the Nationals drop the first of a three-game set to their burgeoning rivals. (Toni L. Sandys/The Washington Post)

The Washington Nationals began their first interleague series of the season with a 2-1 loss to the Baltimore Orioles on Friday night courtesy of Nick Markakis’s home run in the 11th inning before 36,680 at Nationals Park.

The right fielder’s seventh homer of the season came with one out and the count 2-2 against reliever Ryan Mattheus, whose cutter wound up bouncing off the top of the second deck in right field above the Nationals’ bullpen.

The blast sent Washington (23-16), which left two runners on base in the bottom of the 11th, to its second straight loss and third in four games and left starter Edwin Jackson the victim of another hard-luck no-decision despite one of his most robust outings this season.

After allowing a run in the opening inning, Jackson handcuffed the Orioles (26-14) during the rest of his outing. Jackson completed eight innings, surrendering five hits and an earned run with one walk and eight strikeouts on 95 pitches, his second highest total this season.

“That was a tough one,” Nationals Manager Davey Johnson said. “It’s a shame to waste such a great pitching effort by Jackson. He pitched outstanding.”

Baltimore right-hander Jake Arrieta cruised as well, striking out eight over the first five innings and benefiting from the arm of catcher Matt Wieters, who after allowing a stolen base to Ian Desmond in the third threw out two runners at second.

Wieters first picked off Bryce Harper’s steal attempt for the second out of the fourth. One inning later, Wieters wiped Jesus Flores off the docket trying to steal second, and Arrieta struck out Jackson to end the fifth.

The bottom of the sixth began with Arrieta trying to get an 0-1 sinker by Desmond. The Nationals shortstop instead drove the ball into the left field seats roughly a dozen rows deep, and the score was tied at 1.

Desmond’s sixth homer ensured his 15th multi-hit game of the season, the most on the Nationals. He has hit safely in seven of his last eight games with two home runs, four RBI and seven runs scored.

Arrieta regrouped to retire the side in order the rest of the inning without having a ball leave the infield. Arrieta yielded a leadoff single in the seventh to Harper, who reached base on his first three at-bats, before again setting down the side in order with a strikeout and two popups in foul territory.

Arrieta’s night was complete after that inning, and the Orioles’ opening day starter had recovered impressively from his last two outings in which he allowed 13 combined earned runs. His final line included six hits with one walk and nine strikeouts in his most efficient outing since eight scoreless innings against the New York Yankees on May 2.

“Sometimes I feel a little pressure that I put on myself, and it’s just a matter of wanting to go out there and not let your teammates downs,” Arrieta said. “I know that they don’t feel that way, but if I’m able to go out there and pitch like I can on a consistent basis, we’re going to come out on top more times than not.”

Jackson, meantime, logged his best start since giving up no runs over 62 / 3 innings on April 26 against San Diego. He also fell one strikeout short of matching his season high and worked at least five innings for the 98th time in his last 104 starts dating from 2009.

It also was the second time this season Jackson has pitched at least eight innings. His only other such performance came on April 14, when the right-hander’s two-hitter on 92 pitches against Cincinnati sparked the Nationals to a 4-1 triumph and his only victory this season.

Jackson did run into trouble early against Baltimore, walking leadoff hitter Xavier Avery on six pitches. J.J. Hardy flied out to right field, but Markakis lined a double into the gap in left center that left Avery standing on third base.

Adam Jones provided the first run of the game by following with a single that caromed straight up off the pitcher’s mound and dropped in the infield. Avery scored on the peculiar hit, and Markakis advanced to third base before Jackson got Wieters to ground to shortstop Desmond on a 1-1 count.

Desmond fielded the ball with ease, stepped on second base and threw to Adam LaRoche at first for the double play, allowing Jackson to escape further damage during an inning in which he threw 18 pitches.

“I wouldn’t say we had a ton of opportunities,” said Nationals third baseman Ryan Zimmerman, who went 2 for 5 and had an outstanding catch of a hard line drive in the fifth. “Both pitchers threw well. They got a big hit. Nick got a huge hit there at the end, but overall a well-played game. We just came out with the loss.”