Sending out newsletter to 3500+ users

Hi Guys,

I've a multisite network with 3500+ sites. I would love to be more engaged with my users and send them newsletters. But I'm affraid of the numbers. Here are my questions:
- Can I just activate e-newsletter and send-out a newsletter to all my members?
- Will this influence my performance?
- Doesn't this blacklist my SMTP server?
- Are there any other tips and tricks I should think of?

Thanks in advance,
Pieter