Chronic renal infusion of GRK4 antisense oligodeoxynucleotides increased sodium excretion and urine volume, and attenuated the increase in arterial blood pressure in spontaneously hypertensive rats.
Does chronic renal infusion of GRK4 antisense oligodeoxynucleotides attenuate arterial blood pressure and improve sodium excretion in spontaneously hypertensive rats?
Suppression of renal GRK4 expression via antisense oligodeoxynucleotides ameliorates hypertension and improves renal sodium handling in a genetic rat model.
Abnormalities in D 1 dopamine receptor function in the kidney are present in some types of human essential and rodent genetic hypertension. We hypothesize that increased activity of G protein–coupled receptor kinase type 4 (GRK4) causes the impaired renal D 1 receptor function in hypertension. We measured renal GRK4 and D 1 and serine-phosphorylated D 1 receptors and determined the effect of decreasing renal GRK4 protein by the chronic renal cortical interstitial infusion (4 weeks) of GRK4 antisense oligodeoxynucleotides (As-Odns) in conscious- uninephrectomized spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar–Kyoto (WKY) rats. Basal GRK4 expression and serine-phosphorylated D 1 receptors were &90% higher in SHRs than in WKY rats and were decreased to a greater extent in SHRs than in WKY rats with GRK4 As-Odns treatment. Basal renal D 1 receptor protein was similar in both rat strains. GRK4 As-Odns, but not scrambled oligodeoxynucleotides, increased sodium excretion and urine volume, attenuated the increase in arterial blood pressure with age, and decreased protein excretion in SHRs, effects that were not observed in WKY rats. These studies provide direct evidence of a crucial role of renal GRK4 in the D 1 receptor control of sodium excretion and blood pressure in genetic hypertension.
Sanada et al. (Tue,) conducted a other in Genetic hypertension. GRK4 antisense oligodeoxynucleotides (As-Odns) vs. Scrambled oligodeoxynucleotides was evaluated on Sodium excretion, urine volume, arterial blood pressure, and protein excretion. Chronic renal infusion of GRK4 antisense oligodeoxynucleotides increased sodium excretion and urine volume, and attenuated the increase in arterial blood pressure in spontaneously hypertensive rats.