To determine whether alterations in G protein expression contribute to the adrenergic desensitization in the cardiovascular system. Rats were infused subcutaneously with norepinephrine (NE, 0.1 mg·kg1·h1) for 3 or 6 days using osmotic minipumps. G protein α subunits and their mRNAs were then measured in the aorta and heart by using selective antibodies and cDNA probes with Northern blot, dot blot and Western blot analysis. Infusion of NE for 6 days significantly decreased the levels of Gsα, Giα and Goα in the aorta. The mRNAs for the α subunits were not altered in the aorta. In the atrium and ventricle the level of Gsα (45, 42 kD bands) decreased after NE infusion for 3 days but returned to control levels by day 6, the levels of Giα were unaltered after NE infusion for 3 days but increased significantly by day 6, Goα levels did not change at either days. The level of Gi2α mRNA increased after NE infusion for 6 days and may account for the increase of protein. These results demonstrate that expression of G protein α subunits is altered during cardiovascular desensitization,and suggest that alterations of the α subunits contribute to reduced adrenergic responsiveness, the desensitization is due to the decreased levels of Gsα by 3 days and the increased levels of Giα by 6 days of NE infusion.