GRK4 single nucleotide polymorphisms may be responsible for salt sensitivity and essential hypertension by preventing the natriuretic function of the dopaminergic system.
GRK4 single nucleotide polymorphisms may be responsible for salt sensitivity and essential hypertension by impairing renal dopaminergic function.
PURPOSE OF REVIEW: Defective transduction of the dopamine receptor signal in the kidney has been shown to be important in the pathogenesis of hypertension This review will discuss the genetic mechanism for the defective renal dopaminergic function and the interaction with other gene variant products in the pathogenesis of salt sensitivity and essential hypertension. RECENT FINDINGS: Single nucleotide polymorphisms of G protein-coupled receptor kinase type 4 (GRK4) phosphorylate, desensitize, and diminish the inhibitory action of D receptors on sodium transport in the kidney. Inhibition of GRK4 expression normalizes renal proximal tubule D receptor function in humans and rodents and ameliorates the hypertension in genetically hypertensive rats. Expression of the GRK4 variant, GRK4gammaA142V, produces hypertension and impairs the natriuretic effect of D receptor stimulation in mice. In humans, GRK4 single nucleotide polymorphisms are associated with essential hypertension, particularly salt sensitive hypertension. The prediction of the hypertensive phenotype is most accurate when elements of the renin-angiotensin system and GRK4 are included in the analysis. SUMMARY: GRK4 single nucleotide polymorphisms, by preventing the natriuretic function of the dopaminergic system and by allowing the antinatriuretic function of angiotensin II type 1 receptors to predominate, may be responsible for salt sensitivity. Hypertension develops with additional perturbations caused by the variants of other genes (e.g., alpha-adducin, angiotensin converting enzyme, angiotensinogen, angiotensin II type 1 receptor, aldosterone synthase, 11beta-hydroxysteroid dehydrogenase type 2), the quantitative interaction of which may vary depending upon the genetic background.
José et al. (Sat,) conducted a review in Hypertension. GRK4 single nucleotide polymorphisms was evaluated on Salt sensitivity and essential hypertension. GRK4 single nucleotide polymorphisms may be responsible for salt sensitivity and essential hypertension by preventing the natriuretic function of the dopaminergic system.