The shooting happened on I-440 W between New Bern and Brentwood Road just before 4 a.m. Sunday.
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Officers later found 44-year-old Arlo Dontel Ramsey suffering from a gunshot wound near Hillsborough Street and Glenwood Avenue.
He was taken to WakeMed where he was pronounced dead.
Homicide detectives say a white Chevy Aveo or a white Chevy Sonic hatchback could be connected to the shooting.
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Anyone who was in the area during the early morning hours and may have information that might assist the investigation is asked to call 911 or Raleigh CrimeStoppers at (919) 834-HELP. CrimeStoppers pays cash rewards for anonymous tips that help solve cases.
I-440 W was closed off between New Bern Avenue and Capital Blvd. so officers could search for evidence, officials said.