Adrenergic hyposensitivity during long-term diuretic therapy--a possible explanation for the antihypertensive effect of diuretics?

The long-term effect of hydrochlorothiazide on beta 2-adrenoceptor density on mononuclear cells was investigated in 10 male patients with essential hypertension. There was a 40% reduction in beta 2-adrenoceptor density but no change in receptor affinity. This down-regulation of beta 2-adrenoceptors may explain the observed adrenergic hyposensitivity after long-term diuretic therapy. If lymphocytic beta 2-adrenoceptors represent presynaptic beta-adrenoceptors, a down-regulation of presynaptic beta 2-receptors may occur too, and result in a decrease of adrenergic transmitter release. Under this assumption long-term diuretic treatment causes its antihypertensive effect by modulating adrenergic sensitivity at the receptor level on the presynaptic side leading to an attenuated response to pressor hormones on the postsynaptic vascular side.