BEIRUT – Widespread violence erupted on the streets of Damascus on Wednesday as Syrian security forces and pro-government militias lashed out in revenge for a bombing that killed at least three of the most crucial figures in the nation’s military establishment, calling into question President Bashar al-Assad’s control even over his capital.

The blast targeted a meeting of the top security chiefs charged with overseeing a crackdown against the country’s 16-month-old revolt. The bombing suggesting that the rebels have managed to penetrate the most loyal core of Assad’s inner circle of advisers.

The dead included Defense Minister Dawoud Rajha; Hassan Turkmani, a former minister of defense who headed the regime’s crisis management cell; and Asef Shawkat, Assad’s brother-in-law and deputy chief of staff of the Syrian military.

The government denied news reports that other top figures were also killed in the late morning bombing at the National Security Building in the heart of one of the capital’s most upscale and closely guarded neighborhoods. But the significance of the identities of those confirmed dead was not lost on Syrians or the wider international community.

“It’s obvious that what’s happening in Syria represents a real escalation in the fighting,” U.S. Defense Secretary Leon E. Panetta said Wednesday at a Pentagon news briefing. “This is a situation that is rapidly spinning out of control.”

The rebel Free Syrian Army said its loyalists planted bombs inside a room where the government’s central command unit for crisis management was to meet to discuss efforts to crush the uprising.

The bombs were detonated remotely from outside the building once the meeting was under way, said Col. Malik Kurdi, the rebel group’s deputy commander. “The Free Syrian Army carried out this attack in retaliation for the massacres committed by the regime and because of the international silence,” Kurdi said. “We promised that we are going to hit the regime in its most sensitive axis. This was necessary for us.”

The government said others at the meeting were injured. Some news outlets reported that Interior Minister Mohammad Ibrahim al-Shaar was badly hurt and eventually died from his wounds, but the state-run Syrian Arab News Agency said he and another official identified only as Lt. Gen. Hisham were in “stable” condition. The agency was apparently referring to Hisham Bakhtiar, Assad’s national security chief.

The White House said President Obama and Russian President Vladimir Putin discussed the deteriorating situation in Syria by telephone Wednesday morning. Obama cautioned Putin that maintaining Russia’s alliance with the Assad regime would put his country on the “wrong side of history,” press secretary Jay Carney said.

That the bomber was able to penetrate so deeply into the heart of the establishment could have a powerful effect on morale, not only within Assad’s cabinet but also across the ranks of the military and regime supporters who have thus far remained loyal.

Within hours, fresh defections from security services around the country were reported, as well as revenge attacks by Assad loyalists in Damascus. Although the reports could not be immediately confirmed, they demonstrated the potential for the bombing to rapidly accelerate the disintegration of the government, and to trigger even greater chaos.

Damascus residents reported that pro-government militiamen known as shabiha were swarming into the streets of several Damascus neighborhoods, bent on exacting vengeance. According to one eyewitness in the Shaghour neighborhood of the historic walled Old City, militiamen were breaking down doorways and killing families with knives. The man, who asked not to be named, said he was watching scenes of panic from the roof of his building, as both men and children, carrying guns and knives, ran into the street to try to defend the area against the militiamen.

Opposition activist Tareq Saleh of the Revolutionary Leadership Council of Damascus said he was receiving reports of similar killings in the areas of Hajar al-Aswad and Qadam. “Shabiha militias are killing people with knives,” he said. “There are tens of bodies on the streets.”

The information was impossible to corroborate independently, but activists posted videos of what appeared to be three bodies in the streets of Qadam.

“The situation is getting worse by the second,” said a resident of the Qaboun neighborhood who was contacted by Skype and asked not to be identified because he fears for his safety. “Armed people are walking in the streets. I can’t tell who they are or what God they believe in.”

Elsewhere in the capital, the streets were calm but tense, with most shops closed and few people venturing out. “There is so much fear among the people,” Saleh said. “We are expecting massacres.”

There were numerous reports that many army soldiers had defected in the northern province of Idlib and in parts of the flashpoint city of Homs.

According to a Homs activist who calls himself Abu Emad, more than 250 soldiers were seen abandoning their posts in the Old City neighborhood, long a battleground between rebels and the regime. Armored vehicles pulled out and the soldiers fled, he said, some of them joining the rebels and others simply leaving the area. At the same time, Assad loyalists still in position around the edge of the city were shelling the area with renewed intensity, he said.

Hours after Wednesday’s bombing, the Local Coordination Committees, an opposition group, reported heavy clashes between the military and rebel forces in Qaboun. They said helicopters were being used in the attack.

The bombing, which sent a huge plume of smoke over the Damascus skyline, was planned over the last two months, said Kurdi, the Free Syrian Army officer. He said the rebels had information about the regular meetings of the crisis group and were monitoring the movements of the senior officials taking part in the meetings. Kurdi also said there was an earlier plan to poison the food served at these meetings, but that plan fell through in May.

“If you think of a string of pearls, this may be the decisive moment where the string has been cut and we just see the pearls start falling off,” said Amr al-Azm, a professor at Ohio’s Shawnee State University who is also active in the Syrian opposition.

“Right now we are on the cusp. The regime might be able to contain it, or things might unravel completely.”

The Syrian government, in a statement, called the bombing inside the National Security headquarters a “cowardly act” and vowed to “decisively” eliminate opposition forces, “chasing them out of their rotten hideouts wherever they are until clearing the homeland of their evils.”

“If the people think they can force Syria in a certain direction by killing these people, they are delusional,” the Defense Ministry said in a statement that was read on state-controlled television.

A separate claim of responsibility for the bombing came from a little-known group calling itself the Brigade of Islam, which implied that the strike was a suicide attack. It was not immediately possible to verify the claim.

“An improvised explosive device, done by the battalion of the martyrs, which is part of the Brigade of Islam, was used to bomb the building,” the group said in a Facebook posting. “The explosion took place at the time of a meeting of the top criminals and the demon gang which resulted in the death of several people from the pillars of the regime.”

The death of Shawkat, who was married to Assad’s elder sister Bushra, was especially significant because of Shawkat’s standing both as a member of the Assad family and as a key figure in the effort to crush the uprising, Azm added.

“Asef Shawkat was not only a very close member of the Assad family but also a forceful and powerful member of the inner decision-making circle,” Azm said. “He was well known for being brutal, effective and decisive, and he was at the forefront of the fight against the uprising.”

On Tuesday, Syrian opposition groups said their fighters were converging on Damascus. Despite the overwhelming firepower of government troops, rebel forces appeared to hold their ground in several neighborhoods where the fighting was heaviest, according to members of the opposition.

“Our strategy is to bleed down the regime forces and take over government buildings and key places in the capital,” Kurdi said. He denied that the opposition had been sent any heavy weapons.

The intense fighting in the capital marked the first time that many Damascus residents had seen overt signs of the bloody uprising against Assad that has left at least 14,000 Syrians dead.

At the Pentagon, Panetta and visiting British Defense Secretary Philip Hammond said the violence underscores the need for Assad to peacefully cede power, under a transition plan brokered by U.N.-Arab League special envoy Kofi Annan. In London, British Foreign Secretary William Hague condemned the bombing and called on all members of the U.N. Security Council, including Syrian allies Russia and China, to pressure Assad to accept the Annan plan.

“What we’re seeing is an opposition which is emboldened,” Hammond said. “It’s important that both sides understand that the international community is eager to see an orderly transition of power.”

But Russian Foreign minister Sergei Lavrov dismissed such demands, saying they were “rooted in hopelessness.”

“Assad will not go on his own,” Lavrov said, in remarks reported by the Interfax news agency. “Our Western partners, in my opinion, just do not know what to do next. Hence their emotional rhetoric: “If only Russia will stop supporting him!”‘

In a message posted on Twitter, Russian Deputy Foreign Minister Gennady Gatilov condemned Wednesday’s bombing and said it would undermine Security Council deliberations. “A dangerous trend: while the UN SC is discussing the settlement of the Syrian crisis, militants are intensifying terror attacks, disrupting all attempts.”

In a separate statement Wednesday, Russian Foreign Ministry spokesman Alexander Lukashevich said: “Moscow strongly condemns all forms and manifestations of terrorism. We hope the masterminds of the terrorist attack in Damascus will be found and brought to justice.”

At the United Nations, the Security Council delayed a vote on a new Syria resolution until Thursday in a last-minute effort to get key Western nations and Russia to reach agreement on measures to end the violence, the Associated Press reported.

Annan urged the council to delay Wednesday’s scheduled vote after the Damascus bombing, AP said. Ambassadors from the five veto-wielding permanent council nations – the United States, Russia, China, Britain and France – met behind closed doors to discuss Annan’s request, and the Russian envoy later told reporters that the vote was postponed.

Russia argues that Annan has considerable support within some sectors of the Syrian population, and that it is up to Syria to decide its own fate. Russian officials have maintained that their country is not supporting Assad, but is opposed to his being forced from office by international pressure.

The tough Western-backed resolution under consideration Wednesday is in “direct support” of the rebels, and amounts to interference in Syria’s internal affairs, Lavrov said, according to the RIA Novosti agency.

Lavrov met with Annan in Moscow Monday and Tuesday, and Annan also met with President Vladimir Putin. Lavrov said he urged Annan to convene another round of talks on Syria, as a follow-up to last month’s session in Geneva, but this time including Iran and Saudi Arabia.

Lavrov had said Monday, before his meeting with Annan, that he thinks the Western powers are trying to “blackmail” Russia into agreeing to a resolution.

In Washington, White House officials insisted Wednesday that the bombing showed Assad’s hold on power weakening and that the rebel forces were making strides militarily. They blamed the escalating violence on Assad, reiterated the administration’s position that he must relinquish power and rejected the notion that Obama would face increased international pressure to take bolder action.

During his daily news briefing, Carney, the White House spokesman, outlined the morning’s phone call between Obama and Putin and noted that the two leaders discussed the deteriorating situation in Syria last month during a bilateral meeting at the Group of 20 summit in Los Cabos, Mexico. In that meeting, Obama pressed Putin to support establishing a “political process” that would prepare the country for a democratic government, though Putin expressed concerns about potential complications during a transition that could lead to further violence and chaos.

“We do not believe that violence is the answer, and it is precisely because of the ongoing campaign by President Assad against his own people that we are seeing a situation getting worse and worse,” Carney told reporters. “And that is why it is so important for the international community to come together around a plan that produces the political transition that is essential if Syria is to have a brighter future. The incident today makes clear that Assad is losing control, that violence is increasing rather than decreasing, and all of our partners internationally need to come together and support a transition.”

Apparently referring to Russia and China, Carney said that “one concern expressed by those who are resistant to supporting a transition” is that the removal of Assad “would cause the situation to spiral out of control or cause chaos.” He added, “Our position has always been that the situation with Assad in power causes greater violence, greater chaos, and that has been borne out.”

Replying to a question about Assad’s whereabouts and whether he was the target, Carney said: “I don’t have any information on that. We’re still gathering details on the incident.”

Asked about mounting concerns regarding Syrian chemical weapons, he said, “We believe Syria’s chemical weapons stockpile remains under Syrian government control.”

The Obama administration on Wednesday imposed financial sanctions against 29 senior officials in Assad’s government, as well as companies tied to the Syrian agency “responsible for developing and producing non-conventional weapons and the missiles to deliver them,” according to the Treasury Department. Since the start of the uprising in Syria, the administration has now sanctioned more than 100 other individuals and entities in the country.

The measures freeze any assets the individuals or entities may hold in the United States and prohibit U.S. companies from working with them.