Ah, sorry, I see that you're doing this all with a PC based simulator.
If you can take off and pressurize the plane with the cargo door open then the simulator is wrong. If the plane is pressurized the cargo area is pressurized - the floor is not air tight, in fact there have been incidents due to the floor not being open enough to air flow as loss of pressurization in the cargo hold lead to collapse of the floor, taking the control cables out:
http://aviation-safety.net/database/record.php?id=19720612-0
http://libraryonline.erau.edu/online-full-text/ntsb/aircraft-accident-reports/AAR73-02.pdf
A quick back of the envelope calculation:
ISA pressure at 36,000 feet is 3.3 psi
ISA pressure at 8,000 feet is 11.0 psi (cabin altitude)
The B727-100 main cabin floor area is about 670 square feet. Cruising at 36,000 feet with a cabin altitude of 8,000 feet requires a pressure differential of 7.7 psi. 670 square feet is 96,480 square inches, so the pressure load on the cabin floor would be over 740,000 pounds if the passenger section was pressurized and the cargo section was not - that's more than an Airbus 380.
Remember, animals and cargo are transported down there and neither can handle near vacuum conditions and survive.
The B727-100 fuselage is roughly a cylinder 12 feet in diameter and 62 feet long, so we can calculate another somewhat interesting but pretty useless fact that the additional air needed at 36,000 feet to keep the pressure at 8,000 feet weighs about 270 pounds.
I don't know the actual dimensions of the door in the rear pressure bulkhead of N467US, but as I recall they were typically "Type I" size doors (vs. "Type A" size that you usually enter and exit through on the left side of the plane and "Type III" size like the plugs over the wings). "Type I" size doors are typically used on the right side of the plane for servicing the galleys and lavs, but that's really dependent on the particular plane. (There's also a "Type IV" for planes certified for 9 or fewer passengers.) A "Type I" exit has a minimum size of 24 x 48 inches. Even at 10,000 feet (10 psi outside), had the aircraft been pressurized to 8,000 feet the force on the door would have been 1,152 pounds - no way that it could have been opened, hence the requirement to keep the plane low and unpressurized.
For those that are curious and wonder about some nutball opening a door in flight, this is why it can't be done. In most aircraft the door has to be pulled in first, against cabin pressure. Even the plugs over the wings would require an inward pull of over 5,500 pounds at cruising altitude.
And the implications for the Cooper case ... ?