Dopamine D 1 Receptor and Protein Kinase C Isoforms in Spontaneously Hypertensive Rats

Abstract

Abstract —Dopamine, via D 1 -like receptors, stimulates the activity of both protein kinase A (PKA) and protein kinase C (PKC), which results in inhibition of renal sodium transport. Since D 1 -like receptors differentially regulate sodium transport in normotensive and hypertensive rats, they may also differentially regulate PKC expression in these rat strains. Thus, 2 different D 1 -like agonists (fenoldopam or SKF 38393) were infused into the renal artery of anesthetized normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (n=5 to 6/drug/strain). Ten or 60 minutes after starting the D 1 -like agonist infusion, both the infused kidney and the noninfused kidney that served as control were prepared for analysis. The D 1 -like agonists produced a greater diuresis and natriuresis and inhibited Na + ,K + -ATPase activity in proximal tubule (PT) and medullary thick ascending limb (mTAL) to a greater extent in WKY (Δ20±1%) than in SHR (Δ7±1%, P <0.001). D 1 -like agonists had no effect on PKC-α or PKC-λ expression in either membrane or cytosol but increased PKC-θ expression in PT in both WKY and SHR at 10 minutes but not at 60 minutes. However, membranous PKC-δ expression in PT and mTAL decreased in WKY but increased in SHR with either 10 or 60 minutes of D 1 -like agonist infusion. D 1 -like agonists also decreased membranous PKC-ζ expression in PT and mTAL in WKY but increased it in PT but not in mTAL in SHR. We conclude that there is differential regulation of PKC isoform expression by D 1 -like agonists that inhibits membranous PKC-δ and PKC-ζ in WKY but stimulates them in SHR; this effect in SHR is similar to the stimulatory effect of norepinephrine and angiotensin II and may be a mechanism for their differential effects on sodium transport.