Abnormal regulation of renal proximal tubule Na(+)-K(+)-ATPase by G proteins in spontaneously hypertensive rats.
Enhanced salt reabsorption by the kidney, which may arise from impaired regulation of proximal tubule Na(+)-K(+)-ATPase activity, has a central role in the pathogenesis of essential hypertension. Guanine nucleotide binding proteins (G proteins) are involved in many regulatory pathways and have been implicated in the regulation of proximal tubule Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. The present study was designed to evaluate further the regulation of Na(+)-K(+)-ATPase activity by G proteins in proximal tubule suspensions from Wistar-Kyoto rats (WKY) and to determine whether such regulation is abnormal in spontaneously hypertensive rats (SHR). Cholera toxin (CTX) inhibited Na(+)-K(+)-ATPase activity by approximately 40% in WKY but had no effect on Na(+)-K(+)-ATPase activity in SHR. In WKY, pretreatment of tubules with pertussis toxin (PTX), followed by the application of dopamine, inhibited Na(+)-K(+)-ATPase activity significantly, compared with the inhibition produced by dopamine alone. In SHR, dopamine alone did not inhibit Na(+)-K(+)-ATPase activity. However, in the presence of PTX, dopamine inhibited Na(+)-K(+)-ATPase activity significantly. These studies indicate that the renal proximal tubule Na(+)-K(+)-ATPase in WKY is regulated by both a PTX- and CTX-sensitive G protein(s) and that this regulation is abnormal in SHR. Such a defect could cause enhanced sodium reabsorption in SHR and contribute to the pathogenesis of hypertension in this model.
Gurich
R W
RW
Division of Nephrology, University of Texas Medical Branch, Galveston 77555.
Beach
R E
RE
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006706:Homeostasis; D006973:Hypertension / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine