Both central and peripheral dopamine (DA) has been shown to play a role in the regulation of blood pressure. Using sensitive nuclease protection analysis, we have compared the expression of DA D-2 receptor (D2-R) mRNA splice variants in brain and pituitary of spontaneously hypertensive rats (SHR) with normotensive Wistar-Kyoto (WKY) controls. Levels of D2-R mRNA were significantly altered in pituitary anterior lobe (AL) and neurointermediate lobe (NIL), and in striatum of SHR, but not in any other brain regions examined. SHR pituitary expressed 50-80% higher levels of D2-R mRNA, coupled with an increase in the relative proportion of the long (D2-L) mRNA variant. In contrast, overall D2-R mRNA expression in SHR striatum was only 75% that of WKY controls, however, the relative proportion of the D2-L splice variant was increased. The present data demonstrate that tissue specific alterations in D2-R mRNA levels and primary transcript splicing exist in the SHR and suggest that these changes may in part mediate differential responsiveness to DA that may be related to the development of hypertension.