Title

Dopamine D1 receptor and protein kinase C isoforms in spontaneously hypertensive rats

Document Type

Journal Article

Publication Date

1-1-1998

Journal

Hypertension

Volume

32

Issue

6

DOI

10.1161/01.HYP.32.6.1049

Keywords

Kidney tubules, proximal; Protein kinase C; Receptors, dopamine; Renal medulla

Abstract

Dopamine, via D1-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 D1-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 D1-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 D1-like agonist infusion, both the infused kidney and the noninfused kidney that served as control were prepared for analysis. The D1-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). D1-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 D1-like agonist infusion. D1-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 D1-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.

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