This is a great topic, I'll share a bit of what I've experienced in playing with many, many different configurations of the Bulldog and Extreme .457 platforms .....I'll assume we are talking within the confines of an un-tethered gun. If tethering, there is nothing to discuss YES, regulate if you have the ability!!!!
After regulating, if high pressure capacity isn't enough to yield more than 3 or so shots, then I'm not sure how much you are gaining by going regulated. Even with wide open, >or = to bore sized porting, one should be able to achieve 3 or so shots across a tight ES with most big bores.
it all boils down to available high pressure storage after creating your plenum. I'm sure there is a rule of thumb that could be developed. Just shooting from the hip her if you will--- If you want 5+ flat shots in the upper end of the energy spectrum on a given platform, IMO you will need 3x plenum capacity or greater ratio of high pressure storage to plenum to make regulating worthwhile..
Again, great topic. My $.02 isn't intended to discourage anyone from going down this path, just adding some anecdotal information obtained by burning through a bunch of nitrogen and lead experimenting in this area.......