D₁ Dopamine receptor signalling defect in spontaneous hypertension

Abstract

Dopamine modulates cardiovascular function by actions in the central and peripheral nervous system, by altering the secretion/release of prolactin, pro-opiomelanocortin, vasopressin, aldosterone, and renin, and by directly affecting renal function. Dopamine produced by the renal proximal tubule exerts an autocrine/paracrine action via two classes of dopamine receptors, D1-like (D1 and D5) and D2-like (D2, D3, and D4), that are differentially expressed along the nephron. The autocrine/paracrine function of dopamine, manifested by tubular rather than by haemodynamic mechanisms, becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension. The molecular basis for the dopaminergic dysfunction in hypertension may involve an abnormal post-translational modification of dopamine receptors.

Dopamine, hypertension and obesity

“…Recent experiments showed that the NO system positively influences the D 1A expression, by increasing the receptor synthesis, either under hypoxia conditions or not. 40 In addition, acute inhibition of NO synthesis is related to a decrease in the DA excretion in urine, 27 which showed a positive relation between these two systems.…”

“…26 The D 5 /D 1 ratio in nephron is insignificant, therefore DA actions related to the D 1 (D 1 -like) family are normally attributed to D 1 . 24,27 As far as D 2 -like receptors are concerned, D 3 is expressed in proximal tubules and juxtaglomerular cells. It inhibits renin release by decreasing cAMP, as opposite to D 1 activation, which results in renin release.…”

Dopamine-Mediated Inhibition of Renal Na,K-ATPase Is Reduced by Insulin

“…6 -12 It has been reported that a defect in DA receptor function might contribute to hypertension in animal models as well as in human essential hypertension. 5,[13][14][15] For example, DA fails to inhibit NHE and NKA activities in the spontaneously hypertensive rat, and the natriuretic and diuretic response to exogenously administered as well as endogenous DA is also diminished in this model of hypertension. 16,17 The molecular mechanism for this defect appears to be hyperphosphorylation of the D1 receptor caused by an increase in the constitutive activity of G-protein-coupled receptor kinase (GRK4) in proximal tubular epithelial cells from patients with essential hypertension.…”

Arterial Blood Pressure and Renal Sodium Excretion in Dopamine D3 Receptor Knockout Mice

“…It has been reported that dopamine receptors are involved in the development of hypertension (1). Several experiments have shown that a deletion of the D1-like as well as the D2-like receptors is associated with high blood pressure levels (3).…”

“…It has been suggested that alterations in the dopaminergic system may be involved in the development of hypertension (1).…”