The role of DA1- and DA2-receptors in the control of blood pressure.

1. Endogenous dopamine, acting through specific receptors on blood vessels, renal tubules and adrenal cortical cells, may play a role in the development and maintenance of the hypertensive state. 2. In hypertensive patients, activation of the DA1-receptor with intravenous fenoldopam produces a rapid and sustained reduction in blood pressure, in contrast to the tachyphylaxis seen in some rat models. 3. Activation of the DA2-receptor also represents a viable antihypertensive approach, based on the chronic efficacy of hydergine. However, none of the recently developed selective DA2-receptor agonists has been shown to reduce blood pressure in man. 4. Since animal experiments suggest qualitatively different antihypertensive profiles for quinpirole and SK&F 101468, both presumed to be selective agonists at the DA2-receptor, it may be possible to design new DA2-receptor agonists more effective as antihypertensive drugs. 5. Dopamine receptors at different sites, even if of the same subtype, can be differentially regulated; this may be a consequence of activation of multiple second messenger systems by receptor occupation.