Most people who send end user domain sales emails use Whois information to contact potential buyers. People use services like LeadRefs and Estibot to “harvest” email addresses of potential buyers, and while both of these services are valuable, without purging some of the email addresses, you run the risk of annoyance.
Although most people have sold obscure domain names for high prices when people have inquired, it’s rare that you’ll be able to sell an obscure domain name to a domain investor unless there are extenuating circumstances. Unless a domain investor has a great interest in a particular topic, it’s unlikely that he’ll be interested in a very specific domain name (like ReconstructiveOrthopaedics.com for example).
I’ve personally found that most domain investors these days are generally only buying great domain names on the aftermarket. From this experience, I generally shy away from sending emails to other domain investors on names that are for niche verticals and would only excite people who are in that line of business.
One thing you should do if you are selling domain names using Whois email contacts is to learn the Whois information of domain investors (like Mike Berkens and Frank Schilling), privacy services (like Go Daddy’s Domains By Proxy), hosting companies (like BlueHost), and large domain investment companies (like Huge Domains and Buy Domains).
I don’t usually mind receiving emails offering very good domain names for sale, but there are some people who constantly send me crap, and I don’t even read their emails anymore. If someone marks you down as a spammer, they will likely ignore all of your emails.
With tough economic times and domain investors rarely buying average names on the aftermarket, I would become familiar with their Whois information and purge their email addresses from your sales lists.